Molecular mechanisms and Th1/Th2 pathways in corticosteroid regulation of cytokine production

We focus on how the IL-I system, T-halper1 (Th1) or Th2 cytokines and glucocorticoids, converge to give a unified physiological response. Glucocorticoids inhibit IL-I and IL-1 receptor antagonist (IL-1ra) expression, Th1 cytokines stimulate both and Th2 cytokines stimulate IL-1ra and inhibit IL-1. Thus, during the Th1 response there is a window for IL-1 inflammatory activity, absent during the Th2 response. We also study the interactions among glucocorticoid and cytokine transcriptional activity. Glucocorticoids inhibit cytokine induced transcription factors (NFkB, AP1) and cytokines enhance glucocorticoid receptor (GR) transcriptional activity, thus reciprocally fine tuning immunological control mechanisms. (C) 2000 Elsevier Science BN. All rights reserved.