Dexamethasone promotes type 2 cytokine production primarily through inhibition of type 1 cytokines

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
S K Agarwal, G D Marshall

Abstract

Glucocorticoids, at concentrations mimicking stress-physiologic plasma levels, cause an in vitro shift in the type 1/type 2 cytokine balance of human peripheral blood mononuclear cells (PBMC) toward a predominant type 2 response. The mechanisms of these immune alterations are currently unknown but may involve modulation of key cytokines known to regulate the type 1/type 2 cytokine balance. Therefore, we sought to determine the role of cytokines previously reported to regulate the type 1/type 2 cytokine balance, including interleukin-12 (IL-12), interferon-gamma (IFN-gamma, IL-10, IL-4, and IL-13, in the glucocorticoid-mediated human type 1/type 2 cytokine alterations. Human PBMC were stimulated in vitro with tetanus toxoid in the presence of 10(-8) M dexamethasone (DEX). Cultures were supplemented with recombinant human (rHuIL-12), rHuIFN-gamma, or neutralizing monoclonal antibodies (mAb) against IL-4, IL-10, or IL-13. DEX decreased IFN-gamma production and increased IL-4 and IL-10 production by tetanus-stimulated PBMC. The addition of either recombinant IL-12p70 or IFN-gamma abrogated the DEX-mediated decrease in IFN-gamma and increase in IL-4 production. Neutralization of IL-4 activity partially abrogated the DEX-induced alte...Continue Reading

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