Immunotoxicology Specialty Section Newsletter

PresidentDr. Bob Luebke

Vice PresidentDr. Ken Hastings

Vice President-ElectDr. Mitchell Cohen

Secretary-TreasurerDr. Steve Pruett

Councilor/Past PresidentDr. Thomas Kawabata

Senior CouncilorDr. Jeanine Bussiere

CouncilorDr. Michael McCabe

Student RepresentativeDr. Jamie DeWitt

O u t g o i n g P r e s i d e n t ’ s M e s s a g e

The Immunotoxicology Specialty SectionNewsletter is published 3 times/year (May,August and November). If you would like toshare a book review, meeting report, interest-ing web site or any other item of interest withmembers of the Specialty Section, please sendit to us by the middle of the month precedingthe planned publication date. All commentson, or suggestions for, the newsletter are welcome.

Stephen B. Pruett, Ph.D., Editor Department of Cellular Biology and Anatomy LSU Health Sciences Center 1501 Kings Highway Shreveport, LA 71130 Tel. (318) 675-4386 Fax (318) 675-5889 spruet@LSUHSC.EDU

Jean F. Regal, Associate EditorDepartment of Pharmacology10 University Dr.University of MinnesotaDuluth, Minnesota 55812Tel. (218) 726-8950 Fax (218) 726-7906jregal@d.umn.edu

Typesetting provided by Brenda House.

2004 - 2005Executive Committee

May 2005 1 Immunotoxicology Specialty Section

Bob Luebke

Another SOT has come and gone,and once again the Immunotoxi-cology Specialty Section was wellrepresented in CE courses,Symposia, platform and poster ses-sions. Many thanks to the peoplewho developed the CE andSymposium sessions, to all of thespeakers, and to everyone whospent time putting together talksand posters. Thanks also to the2005 ISS Program Committee,Chaired by Ken Hastings, forworking diligently to ensure thatsymposia and CE proposals werein top shape before submission to the SOT program committee, and to DoriGermolec for presenting and supporting the ISS-endorsed programs on theSOT Program Committee.

A new type of program was announced at the Presidents' and Vice-President'smeeting in New Orleans. Historical Highlights sessions will be 90 minuteslong, may have one or more speakers, and are to highlight how various labsand individuals moved toxicology forward. As James Popp put it, the sessionmust recount contributions but should not be structured as a review of onecompound or take on the air of a memorial lecture. We were also reminded thatSOT sponsors (administrative and financial support) Contemporary Topics inToxicology meetings. Members are encouraged to organize CCT meetings andto apply for support . Details can be found on the SOT website:(http://www.toxicology.org/memberservices/meetings/cct_guidelines.html).

At the risk of boring repetition, everyone is encouraged to nominate individualsfor office in the ISS, and to nominate members for awards. As I pointed lasttime, we had only one nomination for the Young Immunotoxicologist Awardand I know that there must be another qualified scientist within our 278 mem-bers. Please see Jeanine Bussiere's Awards Committee report for details onawards for 2005.

A bit of administrative detail: We had a good turnout this year for the ISSbusiness meeting/social hour. In fact, the room was pretty crowded, and we hadoriginally been slated for a room that was about 40% smaller. Headquarters isnow working on allocating space based on membership numbers, so hopefullywe will have more space in the future. I'd appreciate your comments on ourbusiness meeting. Based on the survey Tom Kawabata put together last year,people wanted less formal meeting time and a greater chance to socialize. Arewe meeting that request? Were the reports too long? Was an appropriate

Bob Luebke

Continued on page 2

May 2005 2 Immunotoxicology Specialty Section

Incoming President’sMessageKen HastingsWell, I hope all have recovered fromthe Big Easy experience - I know I'm

going to wait a while before eating oys-ters again. It was a great meeting and Ihope you found it as rewarding as I did.First, let me say what an honor it is toserve as President of the Immunotoxi-cology Specialty Section: this is espe-cially true for someone like me whospends most of his time reading - andadmiring - the work of others in thefield. I really don't get to go into the labanymore (probably a good thing) but

have the task of trying to translate science into what is, for all practicalpurposes, public policy. "Regulatoryscience" is, I think, a particularly arcanespecialty - one that I enjoy but withoutquestion dependent on excellent labora-tory science.

Which brings me to the first item on mylist: NIH funding of immunotoxicologyspecifically, and toxicology generally.Many ISS members have experiencedfrustration with the NIH review process,and particularly the lack of a reasonable"home" for having grants reviewed byscientists qualified to make reasonableand informed decisions. My own hunchis that this situation isn't likely toimprove without significant input fromfolks like you - we need to make surethat our specialty (and toxicology gen-erally) doesn't suffer from lack of ade-quate support. Several of us attended anILSI sponsored meeting a couple ofyears ago on immune-mediated drughypersensitivity reactions - and espe-cially how to ensure that adequate fund-ing is available to deal with this vexingand persistent problem. At one point inthe meeting, the issue of NIAID fund-ing was discussed - and we were toldthat although the Institute recognizeddrug allergy as a serious public healthissue, they were not in a position tofund research in this area. My opinionis that this is short-sighted and arguablyneglecting the mission of the Institute.But my opinion doesn't count for much- only when a committed group of sci-entists pursue a remedy to a problemwill a solution be found.

Many of you have read my reports ondevelopment of an immunotoxicologyguidance document as part of theInternational Conference onHarmonisation (ICH). I suspect manyare not sure exactly what's going onhere and why this effort is important.My apologies to those who alreadyknow this, but ICH is an effort to pro-duce a standard set of expectations fordemonstrating safety and efficacy ofmarketed drug products. Currently,there are six parties involved in thisprocess: the regulatory authorities ofJapan, the European Union, and theUnited States (respectively, the Japan

Ministry of Health, Labour, and Welfare(JMHLW); the European MedicinesEvaluation Agency (EMEA); and theUS FDA) and the pharmaceutical indus-tries of these regions. In addition, manyother regulatory agencies have beeninvolved as observers (as well as theWorld Health Organization - which hasa drug development component). Theidea is to have harmonized guidanceson drug development, including stan-dards for nonclinical studies. Immuno-toxicology is one of the safety topicsthat was accepted for negotiations, pri-marily because of differences in expec-tations between EMEA and FDA onwhat would constitute adequate meth-ods for testing. The primary differenceis that the EMEA Committee forProprietary Human PharmaceuticalsNote for Guidance on 28 day repeat-dose toxicity studies recommends thatall new pharmaceuticals be evaluatedfor immunotoxic potential (using eithera T-dependent antibody response assayor a combination of flow cytometry andan NK cell assay). The FDA Center forDrug Evaluation and Research (CDER)advocates a for cause approach to deter-mining the need for functional immuno-toxicity testing. The position taken bythe JMHLW is similar to theFDA/CDER guidance, but their draftconcept paper was never published.This is why the ICH negotiations havefocused on the issue of unintendedimmunosuppression. Many have askedwhy issues related to drug hypersensi-tivity and drug-induced autoimmunitywere not included in negotiations.Simply put: there is no lack of harmonybetween the various regions on thisissue in general and, more importantly,there are few methods about which tonegotiate. The Expert Working Groupon S8 (the official ICH designation ofthe immunotoxicology guidance) willmeet in Brussels in May where a finalguidance will be discussed.

Finally, I encourage anyone with ques-tions (that I can answer - or at leastknow who could) to contact me. Myoffice number (direct) is (301) 827-5922 and my e-mail ishastingsk@cder.fda.gov. I love to talk,so don't hesitate. - Ken

amount of time dedicated to awards?One last business meeting-related item- the quantity of food ordered for thebusiness meeting. In the last few yearswe have ordered food for fewer peoplethan we expected at the meeting; theper person catering charge was morethan the $15/member dues we pay andfood was always left over at the end ofthe meeting. If you think that the foodorder should be adjusted up or down inthe future, please let me know. Thisisn't exactly the most exciting stuff toput in an outgoing president's message,but it is your time and money….howdo you want spend it?

Finally, thanks for the opportunity toserve as an officer in theImmunotoxicology Specialty Section.It has been an enjoyable and educa-tional experience, and I encourageother members of ISS to get involved.See you in San Diego, if not before.

Bob Luebke

Kenneth Hastings

May 2005 3 Immunotoxicology Specialty Section

Update on NIH StudySection Restructuringby Steve Pruett

An issues forum was organized bythe SOT Task Force on StudySection Restructuring at the SOTmeeting in New Orleans. The formatwas a panel discussion, and themajor stakeholders on this issue wererepresented on the panel. On theencouraging side, Michael Martin (adivision director at the Center forScientific Review, which runs thestudy sections), noted that someproblems had been recognized andthat some degree of "consolidation"was planned to allow immunotoxi-cology and other toxicology applica-tions to be focused in fewer studysections, presumably with the addi-tion of some expertise to these studysections. Dr. David Eaton, whochairs the SOT Task Force, indicatedthat the present practice of using adhoc reviewers to handle toxicologyapplications in study sections that arenot toxicology oriented is not appro-priate. He correctly pointed out thatad hoc members seldom have asmuch influence on a study section asregular members and that ad hocmembers generally are unable tochange the culture of the study sec-tion to value a particular area ofresearch. A representative of NIEHSnoted that the new structure hasmade the job of the Program Staffvery difficult, because they can nolonger attend all the relevant studysection meetings. The SOT TaskForce met with the new Director ofNIEHS, David Schwartz, and theyreport that he is concerned about theissue and willing to work with SOTtoward developing a solution.

On the discouraging side, no com-mitment was expressed by CSR to

implement the only suitable remedyfor this situation, the creation of anew toxicology study section thatwould serve as a home for molecularmechanisms, immunotoxicology,developmental toxicology, cardiovas-cular toxicology, and possibly otherareas. Perhaps even more discourag-ing was the presentation the daybefore the panel discussion by Dr.Pat Mastin (NIEHS), whose dataindicated that only a small number ofimmunotoxicology applications hadbeen scored and none had been fund-ed since the restructuring. Anotherproblem was discussed by one of thepanelists with regard to the criteriathat would be used by CSR to justifya new toxicology study section. Itseems that the number of applica-tions submitted with an investigatorrequest for review by the XNDAstudy section is being used, in part,to estimate the "demand" for anothertoxicology study section. However,immunotoxicologists have learnedafter one submission that their appli-cation will not be assigned toXNDA, and most do not requestXNDA. Thus, it would seem advis-able at present for immunotoxicolo-gists to request XNDA in the coverletter, with the understanding thatmost immunotoxicology applicationswill be assigned to the InnateImmunity and Inflammation studysection (which has only 1 immuno-toxicologist as a regular member).

A colleague of mine here at LSUHealth Sciences Center, Dr. TammyDugas, is a cardiovascular toxicolo-gist. She is organizing a grass rootsletter writing campaign in an attemptto keep attention focused on thisissue until a fair solution is achieved.She has mentioned to me that thisissue is especially acute for newinvestigators in academia, who havea very limited period of time to

secure NIH funding, which is gener-ally required for tenure. Therefore,further study and a gradual "consoli-dation" of study sections is an entire-ly inadequate response. I plan to par-ticipate in this letter writing effort,and I would encourage anyone whomay be affected by this situation todo so as well. Requesting a newstudy section would be appropriate,and investigators who have hadexperience with the new study sec-tion structure are especially encour-aged to write. I believe letters frompersons in government and industrywould be as useful as letters frompersons in academia (maybe evenmore useful), because they wouldindicate that the actions of CSR onthis matter could have broad adverseeffects on human health and econom-ic activity. The following are personsto whom you might consider sendinga letter:

Dr. Antonio ScarpaDirector of CSR (after July 1, 2005)Department of Physiology &Biophysics School of Medicine, E541 Case Western Reserve University Cleveland, Ohio 44l06-4970Toni-scarpa@cswru.edu

Dr. Brent StanfieldActing Director CSR (until July 1, 2005)RKL2 - Two Rockledge Ctr, Room 30166701 Rockledge DrBethesda, MD 20892stanfieb@csr.nih.gov

Dr. Michael MartinDirector, Division of Physiology andPathology, CSRRKL2 - Two Rockledge Ctr, Room 61606701 Rockledge DrBethesda, MD 20892martinm@csr.nih.gov

Continued on page 4

May 2005 4 Immunotoxicology Specialty Section

Awards CommitteeBy Jeanine Bussiere

We had a great round of submissions this year for the best graduate student sub-mission, eight in total. We did not have any submissions for the best postdoctoralsubmission, so first, second and third place prizes were given to the top graduatestudent presentation. After review by seven members of the awards committee,the following awards were given:

First Place: Gautham K. Rao (from MSU in Norbert Kaminski's lab) for a pres-entation entitled "delta 9-Tetrahydricannabinol (delta 9-THC) elicits a calciumelevation in T cells through the TRPC channels."

Second Place: Sabine Teske (from WSU in Paige Lawrence's lab) for a presenta-tion entitled "Increased numbers of neutrophils in dioxin-treated mice infectedwith influenza A virus are caused by an Ah receptor-mediated mechanism that islikely specific to the lung."

Third Place was a tie: Castle Funatake (from OSU in Nancy Kerkvliet's lab) fora presentation entitled "Exposure to TCDD augments expression of CD25 onrecently activated T cells" and Sheung P. Ng (from NYU in Judy Zelikoff's lab)for a presentation entitled "Smoking during pregnancy reduces immune tumorsurveillance mechanisms in the offspring: A toxicological model"

The ISS gave $150, $100 and $50 for first, second and third place, respectivelyand Taylor & Francis matched the prizes. In addition, all winners received a freesubscription to the Journal of Immunotoxicology. Finally, the first place winneralso received a free copy of the Encyclopedia of Immunotoxicology fromSpringer.

For the best immunotoxicology paper of the year award, after a desperate lastcall, we had 8 submissions which were evaluated by the committee. The bestpaper chosen was entitled "Cell proliferation arrest within intrathymic lympho-cyte progenitor cells causes thymic atrophy mediated by the Aryl Hydrocarbonreceptor." by Michael D. Laiosa, Amber Wyman, Francis G. Murante, Nancy C.Fiore, J. Erin Staples, Thomas A. Gasiewicz and Allen E. Silverstone.

The Career Achievement Award was presented to Ian Kimber. Dr. Kimber was recognized for his substantial contributions to immunotoxicology and to the Immunotoxicology Specialty Section. Ian credited several colleagues withimportant roles the accomplishments recognized by this Award.

Unfortunately, we did not receive sufficient nominations for the YoungImmunotoxicologist Award this year. We'd like to encourage all of you to nomi-nate people and papers for these awards, as well as encourage your graduate stu-dents and postdoctoral fellows to apply. Many thanks to the awards committeewho have to do a tremendous amount of work in a very short period of time priorto the annual meeting. Committee members included Tai Guo, Helen Haggerty,Lisa Ryan, Ian Kimber, Michael McCabe, and Prakash Nagarkatti.

AwardsDr. Karl MalikCSRRKL2 - Two Rockledge Ctr,Room 61606701 Rockledge DrBethesda, MD 20892malikk@csr.nih.gov

Dr. David SchwartzDirector, NIEHSP.O. Box 12233RTP, NC 27709schwartzd@niehs.nih.gov

Dr. Anne P. SassamanDirector, Division ofExtramural Res. andTrainingNIEHSMD EC-20P.O. Box 12233RTP, NC 27709Sassama1@niehs.nih.gov

Dr. Pat MastinChief, COSPBNIEHSMD EC-23P.O. Box 12233RTP, NC 27709mastin@niehs.nih.gov

Dr. Elias ZerhouniDirector of NIHBuilding 1-Shannon Bldg,Room 1261 Center DriveBethesda, MD 20892ez26y@nih.gov

Dr. David EatonUniversity of WashingtonAssociate Dean forResearch, School of PublicHealth and CommunityMedicineBox 354695Seattle, WA 98195-4695deaton@u.washington.edu

May 2005 5 Immunotoxicology Specialty Section

IMTOX MIAs

ARE YOU ON THIS LIST??

Just before the meeting in New Orleans, our membership according to SOT stood at 375 individuals. Just after, the officialnumbers on the SOT Website indicated that we now only had 275!! Clearly, some student members have moved on in theircareers, other members have changed their fields of focus, and some have retired. However, there is also the possibilitythat there have been some clerical problems at SOT. The Executive Committee looks forward to keeping our SpecialtySection as one of the top five in membership in SOT and to keep growing.

That said, could you please look over the list below of members who are "MIA" to see if your name or that of a colleagueis there? If so, and you believe there is some mistake, please contact George DeGeorge or Ken Hastings (by e-mail wouldbe best) so that the process to correct the oversight can be started. If your name is there simply because your 2005 dueshave not yet been paid, you can contact SOT (or go to their website) to remedy the problem.

Please feel free to let the Executive Committee know how it can be of any help in this matter or any other issue that youfeel needs to be addressed.

Anderson, Robert S Eyre, Russell, J. Kavanagh, Terrance J. Reid, Lynda

Ansari, Ghulam A. Shakeel Flaherty, Dennis K. Kelman, Bruce J. Riley, M. Gary

Asano, Satoshi Frantz, Jerry D. Kim, Hwan Mook Rockwell, Cheryl E.

Atkinson, John E. Frick-Miranda, M. Suzanne Landsiedel, Robert Rosenthal, Gary J.

Azri-Meehan, Shana Gallucci, Randle M. Lavin Williams, Amy L. Rutkowski, Joseph V.

Ball, Douglas J. Garg, Ramesh Lawrence, David A. Ryu, Heui-Young

Bentivegna, Stephen S. Gelzleichter, Thomas R. Lebrec, Herve N. Shedlofsky, Steven I.

Bezdecny, Steven A. Gilmour Ian M. Legrand, Jean-Jacques Sherwood, Robert L.

Black, Lauren E. Glomot, Remi LeSauteur, Lynne Silverstone, Allen

Blank, James A. Goodman, Gay Li, Daming Singer, Thomas

Bluemel, Joerg Gutting, Bradford W. Li Xinguang Srinivasan, Viny

Booker, Carmen Harrod, Kevin S. Mahaffrey, Kathryn R. Stuart, Bruce O.

Bui, Quang Q. Hayes, Terence J. Maher, Robert W. Taylor, Michael J.

Bunaciu, Rodica P. Heck, Diane Mann, Cynthia Thomas, Peter T.

Camacho, Iris A. Henry, Barbara McCue, Jesica M. Thorne, Peter S.

Cao, Ling Heo, Yong McLain, Daniel E. Thurmond, Linda M.

Dalu, Abraham Hinton, Dennis M. Meade, B. Jean Tsunoda, Marashi

Devanaboyina, Uday S. Holian, Andrij Meyers, Laraine L. Verdon, Sylvie L

Dong, Wumin Holsapple, Michael P. Mortimer, Elisabeth Walsh, Anne C.

Dougherty, Kathleen K. Horn, Thomas L. Murante, Francis G. Willis, Robyn A.

Draper, Ken Howell, Michael D. Narayanan, Padma K. You, Li

Duffy, Jessica E. Jerrells, Thomas R. Ndifor, Anthony M. Zanardi, Thomas A.

Dutczak, William J. Kacham, Raju N.K. Panteleyev, Andrey A. Zelikoff, Judith T.

Esber, Henry Kaminski, Norbert E. Popovic, Marija R. Zheng, Jiang

Exon, Jerry H. Rees, David C. Zwickl, Craig M.

May 2005 6 Immunotoxicology Specialty Section

Dr. Helen Ratajczak has served thespecialty section for the past severalyears by receiving and compiling thelist of immunotoxicology publicationsthat have been published in ournewsletters. Now that she has beenelected Secretary/Treasurer of theSpecialty Section, we need someone tovolunteer to do this important job.

Please contact Helen at hratajcz@rdg.boehringer-ingelheim.com if you wouldbe willing to do this.

Head of Contract Research & Clinical TrialsA biotechnology laboratory specializing in clinical immunology and moleculardiagnostics is recruiting a scientist to manage the company's pharmaceuticalservices program. The laboratory is expanding its services in the areas of cellu-lar immunology, molecular genetics and immunotoxicology. This key execu-tive will have the responsibility to lead a team of scientists in this effort.

Requirements include a PhD, technical experience in molecular immunologyand knowledge of the clinical trials business.

Qualified applicants respond with resume to:

Director of Human ResourcesProGene Biomedical Inc./IBT Reference Lab11274 Renner Boulevard, Lenexa, Kansas 66219ibt@ibtreflab.com

CIT New Fac PositionTenure-Track Faculty Position at Michigan State UniversityThe Center for Integrative Toxicology (CIT) at Michigan State University isaccepting applications for a tenure-track academic year faculty position at theAssistant Professor level. We are seeking candidates with an interest andexpertise in immunotoxicology and/or inflammation as it relates to adverseconsequences of drugs or other chemicals in living systems. Candidates shouldhave a Ph.D. degree in Toxicology or related discipline, postdoctoral researchexperience and demonstrated success in obtaining extramural funding.

The candidate will be jointly appointed in the CIT and in a basic sciencedepartment (e.g., Pharmacology & Toxicology, Biochemistry & MolecularBiology) consistent with his/her expertise and interests. In addition to con-tributing to the CIT, the candidate will have the opportunity to participate inone or more other interdisciplinary research and training programs includingthe National Food Safety and Toxicology Center, the Cell and MolecularBiology Program, the Center for Biological Modeling, the Genetics Programand the Neuroscience Program. The successful candidate will be expected toestablish an independent and extramurally-funded research program and to con-tribute to the teaching and service missions of the department and the CIT.

Interested individuals should send their curriculum vitae, statement of researchinterests and future research plans, and 3 letters of recommendation to: Chair,Faculty Search Committee, Center for Integrative Toxicology, C-231 HoldenHall, Michigan State University, East Lansing, MI 48824. Review of applica-tions will begin on April 1, 2005 and will continue until the position is filled.MSU is an Affirmative Action/Equal Opportunity Institution.

ANNOUNCEMENTS

Program Committee ReportReport from the Program Committee-Mitch Cohen

The following proposals for the 2006 SOTmeeting were recommended by theImmunotoxicology Specialty SectionProgram committee to the SOT Programcommittee.

Indirect Mechanisms of Toxicity:Advancing Our Understanding ofNeuroendocrine - Immune Interactions

Suggested format: Symposium

Chair: Leigh Ann Burns Naas. Co-Chair:Virginia M. Sanders.

Models and Mechanisms ofOccupational/Environmental Asthma

Suggested format: Symposium

Chair: Jean Regal, Co-Chair: Mike Luster.

The Bases for Inter-IndividualDifferences in Susceptibility to AllergicDisease

Suggested format: Symposium

Chair: Ian Kimber, Co-Chair: FrankGerberick.

Immunogenicity of ProteinTherapeutics: Assessment and Impacton Study Design and Interpretation

Suggested format: CE (BASIC)

Chair: Yanli Ouyang, Co-Chair: LynneLeSauteur.

Immunotoxicity Evaluation by ImmuneFunction Tests

Suggested format: Workshop

Chair: Danuta Herzyk, Co-Chair: MichaelHolsapple.

Regulatory Application of the MouseLLNA: New Challenges andOpportunities

Suggested format: Workshop

Chair: Michael Woolhiser, Co-Chair: Greg Ladics.

May 2005 7 Immunotoxicology Specialty Section

Program Committee:

Chair:Steve Pruett spruet@LSUHSC.edu

Barbara Mounho bmounho@amgen.comRaj Krishnaraj rkrishna@UIC.eduGreg Ladics Gregory.S.Ladics@USA.dupont.comLeigh Ann Burns-Naas leighann.burns@pfizer.comMike Woohiser mwoolhiser@dow.comAndrij Holian andrij-holian@Umontana.eduNancy Kerkvliet nancy.kerkvliet@orst.eduYanli Ouyang ouyangY@CDER.FDA.govPramila Singh pramila.singh@rtp.ppdi.comJamie DeWitt (post-doc) dewitt.Jamie@epa.govIan Kimber ian.kimber@syngenta.comDe Facto MembersDori Germolec germolec@niehs.nih.govMitch Cohen cohenm@env.med.nyu.edu

Membership Committee:

Chair:George DeGeorge gdegeorge@MBResearch.com

Marsha Ward ward.marsha@epa.gov

Communications Committee:

Chair (until June 1, 2005):Peyton Myers LMyers@cdc.gov

Chair (after June 1, 2005):Susan McKarns smckarns@niaid.nih.gov

Education Education Committee:

Chair:Judy Zelikoff udyz@env.med.nyu.edu

Raj Krishnaraj rkrishna@UIC.eduTai L. Guo tlguo@hsc.vcu.eduSheung Ng ng@env.med.nyu.eduJamie DeWitt dewitt.Jamie@epa.govCourtney Sulentic Courtney.sulentic@wright.edu

Awards Committee:

Chair:Mike McCabe Michael_mccabe@urmc.rochester.edu

Lisa Ryan ryanlk@umdnj.eduBarbara Mounho bmounho@amgen.comDanuta Herzyk danuta.j.herzyk@gsk.comMichelle Horner mhorner@amgen.comYanli Ouyang Ouyang@CDER.FDA.GovNick Filipov filipov@cvm.msstate.eduSheung Ng ng@env.med.nyu.edu

Regulatory Committee:

Chair:Peter Thomas peter.Thomas@covance.com

Jeanine Bussiere bussierj@amgen.comYanli Ouyang Ouyang@CDER.FDA.govJi-Eun Leeji@cpchem.com

COMMITTEE ROSTERS 2004-2005(from sign up sheets and subsequent contacts)

May 2005 8 Immunotoxicology Specialty Section

Compiled by Helen Ratajczak

ANYTIME you have a new publication to report, please send it to hratajcz@rdg.boehringer-ingelheim.com It will be included in the nextnewsletter.

ASTHMA, ALLERGY AND HYPERSENSITIVITY

Basketter DA, Anderson KE, Liden C, Van Loveren H, Boman A, Kimber I, Alanko K, Berggren E. Evaluation of skin sensitiz-ing potency of chemicals by using the existing methods and considerations of relevance for elicitation. Contact Dermatitis 52:39-43, 2005.

Casati S, Aeby P, Basketter DA, Cavani A, Gennari A, Gerberick GF, Griem P, Hartung T, Kimber I, Lepoittevin J-P, Meade BJ,Pallardy M, Rougier N, Rousset F, Rubinstenn G, Sallusto F, Verheyen GR, Zuang V. Dendritic cells as a tool for the predictiveidentification of skin sensitisation hazard. Alt Lab Animals 33:47-62, 2005.

Fairley KJ, Howell MD, Tomazic VJ, Leakakos T, Truscott W, Meade BJ. Augmented latex specific IgE antibody response inBALB/c mice upon concurrent exposure to natural rubber latex proteins withglutaraldehyde. J Toxicol: Ocular and CutaneousToxicol 23:303-320, 2004.

Hopkins JE, Naisbitt DJ, Kitteringham NR, Dearman RJ, Kimber I, Park BK. Selective haptenation of cellular or extracellularprotein by chemical allergens: association with cytokine polarization. Chem Res Toxicol 18:375-381, 2005.

Howell MD, Tomazic VJ, Leakakos T, Truscott W, Meade BJ. Immunomodulatory effect of endotoxin on the development oflatex allergy. J Allergy Clin Immunol 113:916-924, 2004.

Kimber I, Dearman RJ. What makes a chemical a respiratory sensitizer. Curr Op Allergy Clin Immunol 5:119-124, 2005.

Wacholz PA, Dearman RJ, Kimber I. Detection of allergen specific IgE antibody responses. J Immunotoxicol 1:189-199, 2004.

Reviews

Basketter DA, Patlewicz GY, Smith Pease CK, Gilmour N, Kimber I. Approaches to the predictive identification and assessmentof chemical contact allergens. In: Immune Mechanisms in Allergic Contact Dermatitis. Eds: Cavani A, Girolomoni G, LandesBioscience, Georgetown, pp 1-13, 2005. [Correction of citation listed in Immunotoxicology Specialty Section Newsletter Mar, 2005.]

Cumberbatch M, Dearman RJ, Griffiths CEM, Groves RW, Kimber I. Langerhans cell migration and the induction phase of skinsensitisation. In: Immune Mechanisms in Allergic Contact Dermatitis. Eds: Cavani A, Girolomoni G, Landes Bioscience,Georgetown, pp 29-43, 2005. [Correction of citation listed in Immunotoxicology Specialty Section Newsletter Mar, 2005.]

Kimber I, Dearman RJ. Recent developments in allergic contact dermatitis. In: Investigative Immunotoxicology. Eds: TryphonasH, Fournier M, Blakley BR, Smits JEG, Brousseau P. CRC Press, Boca Raton, pp 291-302, 2005.

Sarlo K, Dearman RJ, Kimber I. Guinea pig, mouse and rat models for safety assessment of protein allergenicity. In:Investigative Immunotoxicology. Eds: Tryphonas H, Fournier M, Blakley BR, Smits JEG, Brousseau P, CRC Press, Boca Raton,pp 269-280, 2005.

AUTISM

Calandrillo SP. Vanishing vaccinations: why are so many Americans opting out of vaccinating their children? U Mi J LawReform 37:353-440, 2004.

Yun AJ, Bazar KA, Lee PY. Pineal attrition, loss of cognitive plasticity, and onset of puberty during the teen years: is it a modernmaladaptation exposed by evolutionary displacement? Med Hypoth 63:939-950, 2004.

Reviews

Ashwood P, Van de Water J. A review of autism and the immune response. Clin Devel Immunol 11:165-174, 2004.

Kennedy RC, Byers, VS, Marchalonis JJ. Measles virus infection and vaccination: potential role in chronic illness and associat-ed adverse events. Crit Rev Immunol 24:129-156, 2004.

R e c e n t I m m u n o t o x i c o l o g y P u b l i c a t i o n s

May 2005 9 Immunotoxicology Specialty Section

CYTOKINES AND CHEMOKINES

Filipov NM, Seegal RF, Lawrence DA. Manganese potentiates in vitro production of proinflammatory cytokines and nitricoxide by microglia through a nuclear factor kappa B-dependent mechanism. Toxicol Sci 84:139-148, 2005.

Martin PL, Cornacoff J, Prabhakar U, Lohr T, Treacy G, Sutherland JE, Hersey S, Martin E. Reviews preclinical safety andimmune-modulating effects of therapeutic monoclonal antibodies to interleukin-6 and tumor necrosis factor- in CynomolgusMacaques. J Immunotoxicol 1:131-139, 2004.

DEVELOPMENTAL IMMUNOTOXICITY

Fukushima T, Kato M, Adachi T, Hamada Y, Horimoto M, Komiyama M, Mori C, Horii I. Effects of sulfasalazine on spermacrosome reaction and gene expression in the male reproductive organs of rats. Toxicol Sci 85:675-682, 2005.

Handley-Goldstone HM, Grow MW, Stegeman JJ. Cardiovascular gene expression profiles of dioxin exposure in zebrafishembryos. Toxicol Sci 85:683-693, 2005.

Latini G, Massaro M, De Felice C. Prenatal exposure to phthalates and intrauterine inflammation: a unifying hypothesis.Toxicol Sci 85:743, 2005.

Loch-Caruso R, Upham BL, Harris C, Trosko JE. Divergent roles for glutathione in lindane-induced acute and delayed-onsetinhibition of rat myometrial gap junctions. Toxicol Sci 85:694-702, 2005.

Vorderstrasse BA, Cundiff JA, Lawrence BP. Developmental exposure to the potent aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs the cell-mediated immune response to infection with influenza A virus, but enhances ele-ments of innate immuity. J. Immunotox. 1(2), 103-112, 2004. [Correction of citation listed in Immunotoxicology SpecialtySection Newsletter Oct, 2004.]

EFFECTS: COMPOUNDS

Brown JM, Pfau JC, Pershouse MA, Holian A. Silica, apoptosis, and autoimmunity. J. Immunotoxicol 1:177-187, 2004.

Burns-Naas LA, White Jr KL, McCay JA, Ivett JL, Zorbas M. Immunotoxicity evaluation of nelfinavir in rats. Human and ExpToxicol 24:67-78, 2005.

Ezendam J, Vos JG, Pieters R. Research articles mechanisms of hexachlorobenzene-induced adverse immune effects in BrownNorway rats. J Immunotoxicol 1:167-175, 2004.

Nishimura N, Yonemoto J, Nishimura H, Ikushiro S, Tohyama C. Disruption of thyroid hormone homeostasis at weaning ofHoltzman rats by lactational but not in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 85:607-614, 2005.

Ravel G, Christ M, Perron-Lepage M-F, Condevaux F, Descotes J. Trichloroethylene does not accelerate autoimmune diabetesin NOD mice. J Immunotoxicol 1:141-148, 2004.

Ruby CE, Funatake CJ, Kerkvliet NI. 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) directly enhances the maturation and apopto-sis of dendritic cells in vitro. J Immunotoxicol 1:159-166, 2004.

Van Duursen MBM, Sanderson JT, Van den Berg M. Cytochrome P450 1A1 and 1B1 in human blood lymphocytes are not suit-able as biomarkers of exposure to dioxin-like compounds: polymorphisms and interindividual variation in expression andinducibility. Toxicol Sci 85:703-712, 2005.

Volz DC, Bencic DC, Hinton DE, Law JM, Kullman SW. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces organ- specificdifferential gene expression in male Japanese medaka (Oryzias latipes). Toxicol Sci 85:572-584, 2005

Yoshizawa K, Marsh T, Foley JF, Cai B, Peddada S, Walker NJ, Nyska A. Mechanisms of exocrine pancreatic toxicity inducedby oral treatment with 2,3,7,8 tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats. Toxicol Sci 85:594-606. 2005.

May 2005 10 Immunotoxicology Specialty Section

EFFECTS: ENVIRONMENT

Dunn JS, Freed BM, Gustafson DL, Stringer KA. Inhibition of human neutrophil reactive oxygen species production andp67phox translocation by cigarette smoke extract. Atherosclerosis 179:261-7, 2005.

Schlezinger JJ, Howard GJ, Hurst CH, Emberley JK, Waxman DJ, Webster T, Sherr DH. Environmental and endogenous peroxi-some proliferator-activated receptor gamma agonists induce bone marrow B cell growth arrest and apoptosis: interactionsbetween mono(2-ethylhexyl)phthalate, 9-cis-retinoic acid, and 15-deoxy-Delta12,14-prostaglandin J2. J Immunol 173:3165,2004.

Stringer KA, Freed BM, Dunn JS, Sayers S, Gustafson DL, Flores SC. Particulate phase cigarette smoke increases MnSOD,NQO1, and CINC-1 in rat lungs. Free Radic Biol Med 37:1527-1533, 2004.

Reviews

Corsini E, Kimber I. Chemical allergy. In: Pollutants and their Impact on Human Body. Eds: Coman G, Draghici C. EdituraUniversitatii Transilvania Brasov, Brasov, pp 63-68, 2004.

GENETICS AND IMMUNOLOGY

Moggs JG, Murphy TC, Lim FL, Moore DJ, Stuckey R, Antrobus K, Kimber I, Orphanides G. Anti-proliferative effect of estro-gen in breast cancer cells that re-express ERx is mediated by aberrant regulation of cell cycle genes. J Mol Endocrinol 34:535-551, 2005.

Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X. Genotoxic effects on spermatozoa ofcarbaryl-exposed workers. Toxicol Sci 85:615-623, 2005.

MODELS AND METHODS

Furst SM, Komocsar WJ, Khan KN, White KL, PeacheeVL, Mennear JH. Screening new drugs for immunotoxic potential: I.Assessment of the effects of conventional nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors on in vitro and invivo phagocytic activity. J of Immunotox 1:149-158, 2004.

Matheson JM, Johnson VJ, Vallyathan V, Luster MI. Exposure and immunological determinants in a murine model for toluenediisocyanate (TDI) asthma. Toxicol Sci 84:88-98, 2005.

Matheson JM, Johnson VJ, Luster MI. Immune mediators in a murine model for occupational asthma: Studies with toluenediisocyanate. Toxicol Sci 84:99-109, 2005.

Rhomberg LR. Seeking optimal design for animal bioassay studies. Toxicol Sci 84: 1-3, 2005.

Slob W, Moerbeek M, Rauniomaa E, Piersma AH. A statistical evaluation of toxicity study designs for the estimation of thebenchmark dose in continuous endpoints. Toxicol Sci 84: 167-185, 2005.

Van de Bovenkamp M, Groothuis GMM, Draaisma AL, Merema MT, Bezuijen JI, van Gils MJ, Meijer DKF, Friedman SL,Olinga P. Precision-cut liver slices as a new model to study toxicity-induced hepatic stellate cell activation in a physiologicmilieu. Toxicol Sci 85:632-638, 2005.

GENERAL IMMUNOTOXICOLOGY

Bonito RF, de Oliveira NM, Nishioka Sde A. Adverse reactions associated with a Fuenzalida-Palacios rabies vaccine: a quasi-experimental study. Revista Da Sociedade Brasileira de3 Medicina Tropical 37:7-9, 2004.

Carter CR, Dagg BM, Whitmore KM, Keeble JR, Asokanathan C, Xing D, Walker KB. The effect of pertussis whole cell andacellular vaccines on pulmonary immunology in an aerosol challenge model. Cellular Immunol 227:51-58, 2004.

May 2005 11 Immunotoxicology Specialty Section

May 2005 12 Immunotoxicology Specialty Section

Cooper CL, Davis HL, Morris ML, Efler SM, Krieg AM, Li Y, Laframboise C, Al Adhami MJ, Khaliq Y, Seguin I, CameronDW. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine 22:3136-3143,2004.

Eichler TE, Ransom RF, Smoyer WE. Differential induction of podocyte heat shock proteins by prolonged single and combina-tion toxic metal exposure. Toxicol Sci 84:120-128, 2005.

Geier DA, Deier MR. Gastrointestinal reactions and rotavirus vaccination based upon analysis of the Vaccine Adverse EventsReporting System (VAERS) database for 1999. A model for the calculation of the incidence rates and statistical significance ofadverse events following immunization. Hepato-Gastroenterol 51:465-469. 2004.

Geier MR, Gerier DA. Gastrointestinal adverse reactions following anthrax vaccination: an analysis of the Vaccine AdverseEvents Reporting System (VAERS) database. Hepato-Gastroenterol 51:762-767, 2004.

Gomber S, Sharma R, Ramachandran VG. Immunogenicity of low dose intradermal hepatitis B vaccine and its comparison withstandard dose intramuscular vaccination. Indian Pediat 41:922-926, 2004.

He R, Adonov A, Traykova-Adonova M, Cao J, Cutts T, Grudesky E, Deschambaul Y, Berry J, Drebot M, Li X. Potent andselective inhibition of SARS coronavirus replication by aurintricarboxylic acid. [erratum appears in Biochem Biophys ResCommun 324:1152-1153, 2004] Biochem Biophys Res Comm 320:1199-1203, 2004.

Jirathitikal V, Metadilogkul O, Bourinbaiar AS. Increased body weight and improved quality of life in AIDS patients followingV-1 Immunitor administration. European J Clin Nutr 58:110-115, 2004.

Meeting report immune-mediated drug hypersensitivity reactions (IDHR) workshop. J Immunotoxicol 1:201-205, 2004.

Mosolits S, Markovic K, Frodin JE, Virving L, Magnusson CG, Steinitz M, Fagerberg J, Mellstedt H. Vaccination with Ep-CAM protein or anti-idiotypic antibody induces Th1-biased response against MHC class I- and II-restricted Ep-CAM epitopes incolorectal carcinoma patients. Clin Cancer Res 10:5391-5402, 2004.

Nurkka A, Joensuu J, Henckaerts I, Peeters P, Poolman J, Kilpi T, Kayhty H. Immunogenicity and safety of the eleven valentpneumococcal polysaccharide-protein D conjugate vaccine in infants. Ped Inf Dis J 23:1008-1014, 2004.

Quaglio G, Pajusco B, Civitelli P, Migliozzi S, Des Jarlais DC, Romano L, Lechi A, Mezzelani P, Lugoboni F. Immunogenicity,reactogenicity and adherence with hepatitis A vaccination among drug users. Drug Alcohol Dependence 74:85-88, 2004.

Sexton K, Lennon D, Oster P, Aaberge I, Martin D, Reid S, Wong S, O'Hallahan J. Proceedings of the meningococcal vaccinestrategy World Health Organization satellite meeting, 10 March 2004, Auckland, New Zealand. New Zealand Med J 117:1 ppreceding U1027, 2004.

Socan M, Frelih T, Janet E, Petras T, Peternelj B. Reactions after pneumococcal vaccine alone or in compbination with influen-za vaccine. Vaccine 22:3087-3091, 2004.

Teske S, Bohn AA, Regal JF, Neumiller JJ, Lawrence BP. Exploring mechanisms that underlie aryl hydrocarbon receptor-medi-ated increases in pulmonary neutrophilia and diminished host resistance to influenza A virus. AJP-Lung Cell Mol Physiol DOI,10.1152/ajplung.00318.2004, 2005.

Yang CY, Lu CY, Lee CY, Shao PL, Wang CY, Wu TZ, Huang LM. An open study of inactivated hepatitis A vaccine (VAQTA inTaiwanese healthy adult volunteers: safety, tolerability, and immunogenicity. M Microbiol Immunol Infect 37:216-218, 2004.

Reviews

Hoffmann S, Hartung T. Diagnosis: toxic! - Trying to apply approaches of clinical diagnostics and prevalence in toxicology con-siderations. Toxicol Sci 85:422-428, 2005.

Ladics GS, Loveless SE. Commentary on hormetic dose-response relationships in immunology: Occurrence, quantitative fea-tures of the dose-response, mechanistic foundations, and clinical implications. Crit Rev Toxicol 35:303-304, 2005.

May 2005 13 Immunotoxicology Specialty Section

Moylett EH, Hanson IC. Mechanistic actions of the risks and adverse events associated with vaccine administration. J AllergyClin Immunol 114:1010-1020, 2004.

Parker GA, Picut C. Liver Immunobiology. Toxicologic Pathol 33:52-62, 2005.

Schwetz BA, Lehman-McKeeman L, Birnbaum LS. Toxicological research involving humans: ethical and regulatory considera-tions. Toxicol Sci 85:419-421, 2005.

Tom WL, Kenner JR, Friedlander SF. Smallpox: vaccine reactions and contraindications. Dermatol Clinics 22:275-289, 2004.

Zimmerman RK, Middleton DB, Burns IT, Clover RD, Kimmel SR. Routine vaccines across the life span. J Fam Pract 54:S9-26, 2005.