The Mighty Corticosteroids

Inflammation (redness, edema, warmth, pain, tissue destruction)

Inflammatory mediators

Leukocyte & endothelial cell activation

Tissue injury Adaptive immune system

Innate immune system

Perceived threat Infection

Corticosteroids

Corticosteroids

Corticosteroids

Corticosteroids

Glucocorticoids Regulate Transcription

GR, glucocorticoid receptor; HSP, heat shock protein; IP, immunophilin;GRE, glucocorticoid receptor

Cortisol

GR HSPHS P

IP

CortisolGR

Cortisol

GR

Cortisol

GRE

NUCLEUS

mRN A

ProteinsmRN A

­ transcription (eg, lipocortin)

or

¯transcription (IL-1, IL-2,

TNF- a, IF- g)GR

Cortisol

Corticosteroids Inhibit Eicosanoid Production

Phospholipase A2

Arachidonic acid

Prostaglandins & thromboxanes Lipoxygenase products (leukotrienes)

Cyclooxygenase (COX) Lipoxygenase

Corticosteroids

inhibit induction

of COX-2 expression

Corticosteroids

Lipocortin

Glucocorticoids Are Powerful Immuno-

suppressants

Corticosteroids affect nearly every facet of immune function, although less inhibition of humoral arm than cell-mediated arm;

they also induce apoptosis in rapidly-dividing leukocytes