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Andreu, G.; Boccaccio, C.; Leguen, J. P.; Oleggini, M. (1992): Ultraviolet light-induced immunomodulation: apossible new tool in organ transplantation. In: Annales de médecine interne, Jg. 143 Suppl 1, S. 52–56.Schlagwörter Adjuvants, Immunologic; Animals; Bloodradiation effects; Humans;

Immunityradiation effects; Organ Transplantation; Ultraviolet Rays

Böhm, M.; Luger, T. A. (2004): [Alpha-melanocyte-stimulating hormone. Its current significance for dermatology].In: Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete, Jg. 55, H. 5, S. 436–445.Online verfügbar unter doi:10.1007/s00105-004-0729-0.Abstract Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that was

originally characterized as a neuropeptide derived from the pituitary gland. alpha-MSH is synthesized from pro-opiomelanocortin (POMC) by the action of specificprohormone convertases which cleave POMC into alpha-MSH, adrenocorticotropinand beta-endorphin. The various effects of alpha-MSH are mediated viamelanocortin receptors. The skin as well as the majority of cutaneous cell typesexpress POMC. Proinflammatory stimuli such as ultraviolet (UV) light induce POMCexpression and alpha-MSH secretion. Receptors for alpha-MSH are not onlyexpressed by melanocytes, where they mediate melanogenesis and proliferation,but also by virtually every cutaneous cell type. Accordingly, alpha-MSH elicits aplethora of biological actions in these cell types including immunomodulation,protection from oxidative stress and UV-induced apoptosis, modulation of secretoryepithelial function and regulation of extracellular matrix composition. These actionsmay be exploited in future by using super potent and truncated MSH peptides forthe treatment of various skin disorders including inflammatory dermatoses.

Schlagwörter Adjuvants, Immunologicmetabolism; Dermatologymethods; Humans;Melanocytesmetabolism; Pro-Opiomelanocortinmetabolism;Skinmetabolismradiation effects; Skin Diseasesdrug therapy; Ultraviolet Rays;alpha-MSHmetabolismtherapeutic use

Byrne, Scott N.; Ahmed, Jarin; Halliday, Gary M.: Ultraviolet B but not A radiation activates suppressor B cells indraining lymph nodes. In: Photochemistry and photobiology, Jg. 81, H. 6, S. 1366–1370. Online verfügbar unterdoi:10.1562/2005-04-20-RA-495.Abstract Immunosuppressive doses of solar-simulated UV radiation activate lymph node B

cells that can suppress primary immunity by inhibiting the function of dendritic cells.The aim of this study was to determine the waveband responsible for activation ofthese suppressor B cells. We exposed C57BL/6 mice to various doses of eitherUVA or UVB radiation and analyzed the number and activation state of lymph nodeantigen-presenting cells (APC). Immunosuppressive doses of UVB but not UVAactivated B cells as assessed by major histocompatibility complex II (MHC II)expression and doubled their numbers in draining lymph nodes. Higher doses ofUVA that were not immunosuppressive actually suppressed B cell activation. Ourresults show that UVA and UVB suppress systemic immunity via differentmechanisms. Lymph node B cells are activated in response to immunosuppressivedoses of UVB but not UVA. Thus, the activation state of lymph node APC appearsto be important for UV immunomodulation.

Schlagwörter Animals; B-Lymphocytescytologyimmunologyradiation effects; DendriticCellscytologyimmunologyradiation effects; Female; Immune Tolerance; LymphNodesimmunology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; UltravioletRays

Cooper, Kevin D.; Baron, Elma D.; Matsui, Mary S. (2003): Implications of UV-induced inflammation andimmunomodulation. In: Cutis; cutaneous medicine for the practitioner, Jg. 72, H. 3 Suppl, S. 11-5; discussion 16.Abstract Sunscreens are the most effective and widely available interventions for sun

damage, other than sun avoidance or clothing. However, sun-screens vary widely intheir ability to screen various UV wavelength components. Testing methods forsunscreens rely on UV-induced erythema to determine a sun protection factor

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - Citavi(SPF), primarily a measure of UVB protection only. Determination of an immuneprotection factor (IPF) has been proposed as an alternative or adjunctive measureto SPF, and, indeed, recent studies show that the IPF can detect the added in vivofunctionality of sunscreens--such as high levels of UVA protection--that the SPFcannot. Consensus on the definition of IPF, however, is required. Data are availableon quantification of the IPF for restoring the afferent or induction arm of contactsensitivity, but other immune parameters also have been measured. A review of invivo studies in humans, in which sunscreens are used to intervene in UV-inducedmodulation of immune response, cells, or cytokines, highlights the technicalvariables and statistical approaches that must be standardized in the context of anIPF for regulatory product claim purposes. Development of such IPF standardswould allow the integration of both UVB and non-UVB solar wave-band effect-reversals. In addition, it could be applied to integrate the effects of other ingredientswith protective function (ie, antioxidants, retinoids, or other novel products) and spurthe development of more advanced and complete protection products.

Schlagwörter Humans; Inflammationetiologyimmunologypathology; Skinimmunologyradiationeffects; Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

Garssen, J.; van Loveren, H. (2001): Effects of ultraviolet exposure on the immune system. In: Critical reviews inimmunology, Jg. 21, H. 4, S. 359–397.Abstract Depletion of stratospheric ozone and changes in lifestyle lead to an increased

exposure to ultraviolet (UV) wavebands, especially in the UVB region (280-320 nm).Besides the beneficial effects of UV exposure, such as vitamin D production,cosmetic tanning, and adaptation to solar UV, UV exposure can also have adverseconsequences on human health, notably sunburn, skin cancer, and ocular damage.Over the last two and a half decades it has become evident that especially UVBexposure and to a lesser extent UVA modulates specific as well as nonspecificimmune responses. Several reports have shown that this immunomodulation playsat least a partial role in the induction of skin cancer. In addition, UVB exposure hasbeen demonstrated to impair resistance to some infections. On the other hand,immunomodulation resulting from UVB exposure might be physiologically importantin inhibiting responses to neoantigens in the skin induced by UV exposure. In thelast 20 years UV has been used frequently as an experimental tool to unravelimmune responses-especially immune responses initiated in the skin (i.e.,photoimmunology). In this review, the major mechanisms responsible for UV-induced immunomodulation and its consequences are summarized.

Schlagwörter Animals; Cytokinesimmunology; Humans; Immune Systemradiation effects;Photoreceptor Cellsimmunology; Ultraviolet Rays

Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Sunlight, immunosuppression and skin cancer: role ofhistamine and mast cells. In: Clinical and experimental pharmacology & physiology, Jg. 28, H. 1-2, S. 1–8.Abstract 1. The development into tumours of skin cells transformed by ultraviolet (UV) B

radiation of wavelengths 290-320 nm is enhanced by the ability of UVB to suppressan immune response that would otherwise destroy them. Ultraviolet B-inducedimmunomodulation may be by multiple mechanisms, but generally manifests in anantigen-presenting cell defect and an altered cytokine environment in the draininglymph nodes. 2. Immune responses to microbial or self-antigens may bedysfunctional by similar mechanisms following UVB exposure. 3. Earliest-actingintermediates in the initiation of UVB-induced immunosuppression are the UVBabsorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatorycytokine production, and trans-urocanic acid (UCA), which, upon isomerization to itscis isomer, signals downstream immunosuppressive events. 4. In mice, dermalmast cells are critical to UVB-induced systemic immunomodulation. In mice, there isa functional link as well as a linear relationship between the prevalence ofhistamine-staining dermal mast cells and the log of the dose of UVB required for50% immunosuppression. Studies with histamine receptor antagonists support

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - Citavihistamine as the main' product of mast cells involved. Histamine acts in large partvia a prostanoid-dependent pathway. 5. Approximately 50% of humans and greaterthan 90% of patients with non-melanoma skin cancer are UVB susceptible forsuppression of a contact hypersensitivity response. Neither cytokine polymorphismsnor UVB-induced levels of cis-UCA in irradiated skin have been linked to UVBsusceptibility. Patients with basal cell carcinomas (BCC) have an increased dermalmast cell prevalence in non-sun-exposed buttock skin. We propose that mast cellsfunction in humans, as in mice, by initiating immunosuppression and, thereby,allowing a permissive environment for BCC development.

Schlagwörter Animals; Carcinoma, Basal Cellimmunologymetabolism; Dermatitis,Contactimmunologymetabolism; Histamineimmunologymetabolismradiation effects;Humans; Immunosuppression; Mast Cellsimmunologymetabolismradiation effects;Mice; Neoplasms, Radiation-Inducedimmunologymetabolism; SkinNeoplasmsimmunologymetabolism; Ultraviolet Raysadverse effects

Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Mast cells in UV-B-induced immunosuppression. In:Journal of photochemistry and photobiology. B, Biology, Jg. 55, H. 2-3, S. 81–87.Abstract Degranulating dermal mast cells in UV-B-irradiated skin have been implicated for

many years in the mechanisms of irradiation erythema. There is now considerableevidence that dermal mast cells are important to the processes by which both UV-Bradiation and cis-urocanic acid (cis-UCA) suppress immune responses tosensitizing antigens applied to non-irradiated/non-cis-UCA-exposed sites. Mast-cell-depleted mice are resistant to the immunosuppressive effects of UV-B radiation andcis-UCA for 'systemic' immunomodulation. However, these mice gainresponsiveness if the dorsal skin is reconstituted six weeks prior to irradiation or cis-UCA administration at that site with cultured bone-marrow-derived mast cells from+/+ mice. The molecular triggers for initiating mast-cell degranulation are beingactively sought. Evidence suggests that histamine, and not tumour necrosis factoralpha, is the major mast-cell product that signals altered immune responses tosensitizing antigens applied to non-irradiated, non-cis-UCA-exposed sites.Histamine may have multiple roles, but experiments with indomethacinadministered to mice have shown that one process involves induction of prostanoidproduction.

Schlagwörter Animals; Bone Marrow Cellscytology; Immunosuppression; Mast Cellsdrugeffectsimmunologyradiation effects; Mice; Skindrug effectsimmunologyradiationeffects; Ultraviolet Rays; Urocanic Acidpharmacology

Hurks, H. M.; van der Molen, R. G.; Out-Luiting, C.; Vermeer, B. J.; Claas, F. H.; Mommaas, A. M. (1997):Differential effects of sunscreens on UVB-induced immunomodulation in humans. In: The Journal ofinvestigative dermatology, Jg. 109, H. 6, S. 699–703. Online verfügbar unter doi:10.1111/1523-1747.ep12340652.Abstract Ultraviolet radiation has been shown to suppress the (skin) immune system both in

animal species and in humans. Whether sunscreens can preventimmunosuppression is a matter of debate. This study investigated the protectivecapacity of a commercial sunscreen lotion in humans. Part of the right arm ofhealthy volunteers was exposed to erythemagenic ultraviolet B doses of 160 mJ percm2 for four consecutive days. Before irradiation, sunscreen was applied eitherdirectly onto the skin or onto a piece of quartz fixed to the skin (to avoid penetrationof the sunscreen in the epidermis where it cannot block the photoisomerization oftrans-urocanic acid in cis-urocanic acid in the stratum corneum). The control groupwas irradiated without prior application of sunscreen. Four h after the lastirradiation, epidermal sheets were obtained by the suction-blister method from botharms and epidermal cells were used as stimulator cells in the mixed epidermal celllymphocyte reaction. Responses directed to epidermal cells derived from irradiatedskin were expressed as percentages of responses directed to epidermal cellsderived from the nonirradiated left arm. The mixed epidermal cell lymphocyte

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - Citavireaction responses in the control group were found to be significantly increased(205%). This enhancement of the mixed epidermal cell lymphocyte reactionresponses was associated with an influx of CD36+DR+ macrophages in theirradiated skin. Application of the sunscreen, either onto a piece of quartz or directlyonto the skin, prevented the increase of the mixed epidermal cell lymphocytereaction responses and the influx of CD36+DR+ cells. In an earlier study,volunteers were exposed three times weekly to suberythemagenic doses ofultraviolet B over 4 wk, resulting in mixed epidermal cell lymphocyte reactionresponses that were decreased to 20%. The same sunscreen was not able toprevent this suppression. These contradicting results indicate that the protectiveeffect of sunscreens with respect to ultraviolet-induced immunomodulation iscritically dependent on the choice of ultraviolet treatment.

Schlagwörter Humans; Lymphocytesdrug effectsradiation effects; Macrophagesdrugeffectsradiation effectsultrastructure; Skindrug effectsimmunologyradiation effects;Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

(1988): Immunomodulation: UV radiation. In: Transplantation proceedings, Jg. 20, H. 1 Suppl 1, S. 302–308.Schlagwörter Animals; Graft Enhancement, Immunologic; Graft Rejectionradiation effects; Graft

vs Host Diseaseprevention & control; Hematoporphyrinspharmacology;Isoantigensimmunology; Lymphocyte Depletion; Mice; T-Lymphocytes,Cytotoxicdrug effectsradiation effects; T-Lymphocytes, Regulatoryradiation effects;Ultraviolet Rays

Luger, T. A.: Immunomodulation by UV light: role of neuropeptides. In: European journal of dermatology : EJD,Jg. 8, H. 3, S. 198–199.Schlagwörter Cells, Cultured; Humans; Immune Systemradiation effects;

Neuropeptidesphysiology; Pro-Opiomelanocortinphysiology; Skinradiation effects;Ultraviolet Rays

Malina, L. (2003): [Urocanic acid and its role in the photoimmunomodulation process]. In: Casopís lékar̆ůc̆eských, Jg. 142, H. 8, S. 470–473.Abstract Urocanic acid (UCA) is a metabolite of the amino acid histidine. It represents an

important chromatophore in epidermis, which can absorb ultraviolet rays in UVBand UVA region and sequentially convert it from trans- to cis-isomer. Cis-isomer isnot further degraded; it accumulates in the skin and is excreted with sweat and inshedding keratin scales. UCA has several important functions, the regulation of thehomeostasis of the acidic cutaneous surface, the terminal differentiation ofepidermal cells and namely the immunomodulatory role. As and immunomodulatorUCA can suppress contact allergic reaction and the delayed hypersensitivity of theorganism. It can affect reactions mediated by Th-lymphocytes, cytokine system,Langerhans cells, and by some neuropeptides. UCA is related to the developmentof non-pigmented skin tumors (basaliomas) and indirectly also to pigmented tumors.Cis-UCA can inhibit both the local and systemic resistance to infectious agents. Inthe immunomodulation some adductive compounds with another importantcutaneous chromatophore DNA can participate.

Schlagwörter Adjuvants, Immunologic; Animals; Humans; Immune Tolerancedrug effectsradiationeffects; Skinimmunologyradiation effects; Ultraviolet Rays; UrocanicAcidimmunologypharmacology

Norman, P. E.; Powell, J. T. (2005): Vitamin D, shedding light on the development of disease in peripheralarteries. In: Arteriosclerosis, thrombosis, and vascular biology, Jg. 25, H. 1, S. 39–46. Online verfügbar unterdoi:10.1161/01.ATV.0000148450.56697.4a.Abstract Vitamin D is generally associated with calcium metabolism, especially in the context

of uptake in the intestine and the formation and maintenance of bone. However,vitamin D influences a wide range of metabolic systems through both genomic andnongenomic pathways that have an impact on the properties of peripheral arteries.

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - CitaviThe genomic effects have wide importance for angiogenesis, elastogenesis, andimmunomodulation; the nongenomic effects have mainly been observed in thepresence of hypertension. Although some vitamin D is essential for cardiovascularhealth, excess may have detrimental effects, particularly on elastogenesis andinflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxicalassociation between arterial calcification and osteoporosis. This review explores therelationship between vitamin D and a range of physiological and pathologicalprocesses relevant to peripheral arteries.

Schlagwörter Animals; Humans; Peripheral Vascular Diseasesepidemiology; Vitamin Dphysiology

Norval, M. (2001): Effects of solar radiation on the human immune system. In: Journal of photochemistry andphotobiology. B, Biology, Jg. 63, H. 1-3, S. 28–40.Abstract On UV irradiation of the skin, a complex cascade of immunological changes results,

initiated by cutaneous chromophores and ending in suppression of some local andsystemic immune responses. In this review, the stages in this process are outlinedfirst, concentrating on the roles of DNA and urocanic acid as photoreceptors.Evidence indicating UV-induced immunomodulation of delayed hypersensitivity andresistance to infectious diseases in human subjects follows. Aspects of geneticsusceptibility to the immunosuppressive effects of UV exposure and extrapolation ofthe data obtained in animal models to the human situation are included. Finallyuncertain and unknown factors relating to the impact of UV on the human immunesystem are discussed.

Schlagwörter Animals; Communicable Diseases; Humans; Hypersensitivity, Delayedimmunology;Immune Systemradiation effects; Immune Tolerance; Immunityradiation effects;Solar Activity; Ultraviolet Raysadverse effects

Pamphilon, D. H.; Alnaqdy, A. A.; Wallington, T. B. (1991): Immunomodulation by ultraviolet light: clinical studiesand biological effects. In: Immunology today, Jg. 12, H. 4, S. 119–123.Abstract The interest of immunologists in ultraviolet (UV) irradiation stems from observations

made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixedlymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy,apparently via suppressor cells and serum factors. At present much interest isfocused on the possible use of UV irradiation to permit transfusion withoutallosensitization and transplantation without either rejection or graft-versus-hostdisease (GVHD). Here, Derwood Pamphilon and colleagues discuss the currentuses and potential of UV irradiation in transfusion and transplantation and relatethese to experimental evidence on its effects at the cellular level.

Schlagwörter Animals; Antigen-Presenting Cellsradiation effects; Antigens, Surfaceradiationeffects; Blood Plateletsimmunologyradiation effects; Blood Transfusion; BoneMarrowimmunologyradiation effects; Bone Marrow Transplantationadverse effects;Calciummetabolism; Cytokinessecretion; Dogs; Graft vs Host Diseaseprevention &control; Humans; Immune Systemradiation effects; Immune Toleranceradiationeffects; Mice; Rats; Secretory Rateradiation effects; TransplantationImmunologyradiation effects; Ultraviolet Rays

Roberts, J. E. (2000): Light and immunomodulation. In: Annals of the New York Academy of Sciences, Jg. 917,S. 435–445.Abstract The immune system is susceptible to a variety of stresses. Recent work in

neuroimmunology has begun to define how mood alteration, stress, the seasons,and daily rhythms can have a profound effect on immune response throughhormonal modifications. Central to these factors may be light through an eye-brainhormonal modulation. In adult primates, only visible light (400-700 nm) is receivedby the retina. This photic energy is then transduced and delivered to the visualcortex and, by an alternative pathway, to the suprachiasmatic nucleus (SCN), thehypothalamic region that directs circadian rhythm. Visible light exposure alsomodulates the pituitary and pineal glands, leading to neuroendocrine changes.

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - CitaviMelatonin, norepinephrine, and acetylcholine decrease with light activation,whereas cortisol, serotonin, GABA, and dopamine levels increase. The synthesis ofvasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), andneuropeptide Y (NPY) in rat SCN has been shown to be modified by light. Theseinduced neuroendocrine changes can lead to alterations in mood and circadianrhythm as well as immune modulation. An alternative pathway for immunemodulation by light is through the skin. Visible light (400-700 nm) can penetrateepidermal and dermal layers of the skin and may directly interact with circulatinglymphocytes to modulate immune function. In contrast to visible light, in vivoexposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can alter normalhuman immune function only by a skin-mediated response. It is therefore important,when reporting neuroendocrine immune findings, to control the intensity, timing andwavelength of ambient light.

Schlagwörter Adult; Humans; Immune Systemphysiology; Neuroimmunomodulation; PhoticStimulation

Sandyk, R. (1993): Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis. In: TheInternational journal of neuroscience, Jg. 68, H. 3-4, S. 209–225.Abstract Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is

age-dependent being rare prior to age 10, unusual prior to age 15, with a peak inthe mid 20s. It has been suggested that the manifestation of MS is dependent uponhaving passed through the pubertal period. In the present communication, I proposethat critical changes in pineal melatonin secretion, which occur in temporalrelationship to the onset of puberty, are intimately related to the timing of onset ofthe clinical manifestations of MS. Specifically, it is suggested that the fall inmelatonin secretion during the prepubertal period, which may disrupt pineal-mediated immunomodulation, may stimulate either the reactivation of the infectiveagent or increase the susceptibility to infection during the pubertal period. Similarly,the rapid fall in melatonin secretion just prior to delivery may account for thefrequent occurrence of relapse in MS patients during the postpartum period. Incontrast, pregnancy, which is associated with high melatonin concentrations, isoften accompanied by remission of symptoms. Thus, the presence of highmelatonin levels may provide a protective effect, while a decline in melatoninsecretion may increase the risk for the development and exacerbation of thedisease. The melatonin hypothesis of MS may explain other epidemiological andclinical phenomena associated with the disease such as the low incidence of MS inthe black African and American populations, the inverse correlation with sun lightand geomagnetic field exposure, the occurrence of relapses in relation to seasonalchanges and fluctuations in mood, and the association of MS with affective illnessand malignant disease. Therapeutically, this hypothesis implies that application ofbright light therapy or the use of other major synchronizers of circadian rhythmssuch as sleep deprivation or application of external weak magnetic fields may bebeneficial in the treatment and/or prophylaxis of relapses in the disease.

Schlagwörter Adolescent; Adult; African Continental Ancestry Group; Age Factors; Age of Onset;Endocrine System Diseasescomplicationsphysiopathology; Female; Humans;Immune Complex Diseasesetiologyphysiopathology; ImmuneSystemphysiopathology; Male; Melatoninsecretion; Middle Aged; MultipleSclerosisetiologyphysiopathologytherapy; Phototherapy; PinealGlandphysiopathology; Puberty

Sleijffers, Annemarie; Garssen, Johan; Vos, Joseph G.; Loveren, Henk (2004): Ultraviolet light and resistance toinfectious diseases. In: Journal of immunotoxicology, Jg. 1, H. 1, S. 3–14. Online verfügbar unterdoi:10.1080/15476910490438333.Abstract Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune

responses in animals and humans. This immunomodulation can lead to positivehealth effects especially with respect to certain autoimmune diseases and allergies.

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - CitaviHowever, UV-induced immunomodulation has also been shown to be deleterious.Experimental animal studies have revealed that UV exposure can impair theresistance to many infectious agents, such as bacteria, parasites, viruses, andfungi. Importantly, these effects are not restricted to skin-associated infections, butalso concern systemic infections. UV radiation induces a multistep process, locallyin the skin as well as systemically, that ultimately leads to immunosuppression. Thefirst event is the absorption of "UV" photons by chromophores, or so-calledphotoreceptors, such as DNA and urocanic acid (UCA) in the upper cell layers ofthe skin. Upon absorption of UV radiation, trans-UCA isomerizes to the cis-isomer.Cis-UCA is likely the most important mediator of UV-induced immunosuppression,as this compound has been shown to modulate the induction of contact typehypersensitivity and delayed type hypersensitivity, allograft rejection, and thefunctions of monocytes and T-lymphocytes as well as natural killer cells. The realconsequences of UV-induced immunomodulation on resistance to infectiousdiseases for humans are not fully known. Risk estimations have been performedthrough extrapolation of animal data, obtained from infection models, to the humansituation. This estimation indicated that UV doses relevant to outdoor exposure canimpair the human immune system sufficiently to have effects on resistance toinfections, but also indicated that human data are necessary to further quantify andvalidate this risk estimation. Further information has been obtained from vaccinationstudies in human volunteers as ethical reasons prohibit studies with infectiousagents. Studies in mice and human volunteers on the effects of prior UVB exposureon hepatitis B vaccination responses revealed suppressed cellular and humoralimmune responses in mice but not in human volunteers. However, subgroups withinthe performed human volunteer study made by determination of cytokinepolymorphisms or UVB-induced mediators, revealed that some individuals havesuppressed hepatitis B vaccination responses after UVB exposure. Thus, it mightbe concluded that the human immune system can be affected by UVB exposure,and decreased resistance to infectious diseases can be expected after sunexposure.

Srinivasan, Venkataramanujan; Spence, D. Warren; Pandi-Perumal, Seithikurippu R.; Trakht, Ilya; Cardinali,Daniel P. (2008): Therapeutic actions of melatonin in cancer: possible mechanisms. In: Integrative cancertherapies, Jg. 7, H. 3, S. 189–203. Online verfügbar unter doi:10.1177/1534735408322846.Abstract Melatonin is a phylogenetically well-preserved molecule with diverse physiological

functions. In addition to its well-known regulatory control of the sleep/wake cycle, aswell as circadian rhythms generally, melatonin is involved in immunomodulation,hematopoiesis, and antioxidative processes. Recent human and animal studieshave now shown that melatonin also has important oncostatic properties. Both atphysiological and pharmacological doses melatonin exerts growth inhibitory effectson breast cancer cell lines. In hepatomas, through its activation of MT1 and MT2receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formationof the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal modelstudies, melatonin has been shown to have preventative action againstnitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growthof prostate tumors via activation of MT1 receptors thereby inducing translocation ofthe androgen receptor to the cytoplasm and inhibition of the effect of endogenousandrogens. There is abundant evidence indicating that melatonin is involved inpreventing tumor initiation, promotion, and progression. The anticarcinogenic effectof melatonin on neoplastic cells relies on its antioxidant, immunostimulating, andapoptotic properties. Melatonin's oncostatic actions include the direct augmentationof natural killer (NK) cell activity, which increases immunosurveillance, as well asthe stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12,and interferon (IFN)-gamma. In addition to its direct oncostatic action, melatoninprotects hematopoietic precursors from the toxic effect of anticancerchemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - Citavibreast cancer, endometrial cancer, or colorectal cancer. The increased incidence ofbreast cancer and colorectal cancer seen in nurses and other night shift workerssuggests a possible link between diminished secretion of melatonin and increasedexposure to light during nighttime. The physiological surge of melatonin at night isthus considered a "natural restraint" on tumor initiation, promotion, and progression.

Schlagwörter Animals; Antineoplastic Agentspharmacology; Cytokinesdrug effectsmetabolism;Humans; Killer Cells, Naturaldrug effectsmetabolism;Melatoninmetabolismpharmacology; Neoplasmsdrug therapyphysiopathology;Receptor, Melatonin, MT1drug effectsmetabolism; Receptor, Melatonin, MT2drugeffectsmetabolism

Suke, Sanvidhan G.; Kumar, Achint; Ahmed, Rafat S.; Chakraborti, Ayanabha; Tripathi, A. K.; Mediratta, P. K.;Banerjee, B. D. (2006): Protective effect of melatonin against propoxur-induced oxidative stress andsuppression of humoral immune response in rats. In: Indian journal of experimental biology, Jg. 44, H. 4, S.312–315.Abstract Effect of melatonin in attenuation of propoxur induced oxidative stress and

suppression of humoral immune response was studied in rats. Oral administrationof propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 daystreatment. Superoxide dismutase, catalase and glutathione were also alteredfollowing propoxur exposure. In addition propoxur exposure markedly suppressedhumoral immune response as assessed by antibody titre and plaque forming cellassay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuatedthe effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and(c) immunotoxicity. Results have been discussed in the light of possibleimmunopotentiating and antioxidant effects of melatonin to understand the influenceof oxidative stress on propoxur induced immunomodulation.

Schlagwörter Animals; Antibody Formationdrug effectsimmunology; Antioxidantsmetabolism;Immunosuppressive Agentspharmacology; Male; Malondialdehydeblood;Melatoninpharmacology; Oxidative Stressdrug effects; Propoxurantagonists &inhibitorspharmacology; Rats; Rats, Wistar

Tran, T. Thanh-Nga; Schulman, Joshua; Fisher, David E. (2008): UV and pigmentation: molecular mechanismsand social controversies. In: Pigment cell & melanoma research, Jg. 21, H. 5, S. 509–516. Online verfügbarunter doi:10.1111/j.1755-148X.2008.00498.x.Abstract Ultraviolet radiation (UVR) is an essential risk factor for the development of

premalignant skin lesions as well as of melanoma and non-melanoma skin cancer.UVR exerts many effects on the skin, including tanning, carcinogenesis,immunomodulation, and production of vitamin D. Vitamin D (vit D) is important inthe maintenance of healthy bones as well as other purported beneficial effects,amongst which is the potential for reducing risk of malignancy--though oralsupplementation is fully capable of maintaining systemic levels. The known medicalharm from UV exposure relates primarily to cancer of the skin--the most commonorgan in man to be affected by cancer. In this review, we summarize the knowledgeabout the ultraviolet (UV) response in regards to inflammation, immunosuppression,carcinogenesis and the tanning response. We also discuss vit D and UV, as well aspublic health implications of tanning behavior and commercial interests related tothe promotion of UV exposure. As the most ubiquitous human carcinogen, UVRexposure represents both a challenge and enormous opportunity in the realm ofskin cancer prevention.

Schlagwörter Humans; Immune Systemradiation effects; Lightadverse effects; Risk Factors;Skinmetabolismpathologyradiation effects; SkinNeoplasmsetiologypathologyphysiopathology; SkinPigmentationphysiologyradiation effects; Ultraviolet Raysadverse effects; VitaminDmetabolism

Wintzen, M.; Yaar, M.; Burbach, J. P.; Gilchrest, B. A. (1996): Proopiomelanocortin gene product regulation in

iLib08 - CitaviiLib08 - CitaviiLib08 - CitaviiLib08 - Citavikeratinocytes. In: The Journal of investigative dermatology, Jg. 106, H. 4, S. 673–678.Abstract Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone,

melanocyte-stimulating hormones, beta-lipotropic hormone (beta LPH), and betaendorphin. These peptides can function as neurotransmitters, modulate immuneresponses, and affect melanogenesis. We investigated POMC expression andprotein processing in normal human keratinocytes. On Northern blot analysis, thebaseline expression of the 1.2-kb POMC transcript was upregulated by ultravioletradiation (UVR) or by stimulation with interleukin-1 alpha (IL-1 alpha) or phorbol 12-tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, beta LPH, andbeta-endorphin were detected in cell extracts under baseline conditions. beta LPHlevel increased substantially after UVR, IL-1 alpha, or TPA. Within 36 h after TPAstimulation, beta-endorphin became undetectable in cell extracts, coinciding with anincrease of beta-endorphin-immunoreactive protein in the culture medium. Our dataestablish that keratinocytes synthesize POMC protein as well as its derivatives betaLPH and beta-endorphin, and that this process is modulated by TPA, IL-1A, andUVR. beta LPH and beta-endorphin of keratinocyte origin may thus be involved inmelanogenesis and/or immunomodulation in the skin after sun exposure, and theirrelease into the circulation may also have systemic effects.

Schlagwörter Cells, Cultured; Gene Expression Regulation; Humans; Interleukin-1pharmacology;Keratinocytesdrug effectsmetabolismradiation effects; Pro-Opiomelanocortinanalysisgenetics; RNA, Messengeranalysis;Tetradecanoylphorbol Acetatepharmacology; Ultraviolet Rays; beta-Endorphinanalysis