Does cortisol bias cytokine production in cultured porcine splenocytes to a Th2 phenotype?
Glucocorticoids are reported to bias the production of cytokines from a type 1 to a type 2 phenotype. However, this dogma has been advanced largely from studies utilizing potent glucocorticoid analogs, particularly dexamethasone (DEX). Although studies utilizing DEX certainly have clinical and pharmacological relevance, DEX is probably not the best glucocorticoid for studies designed to evaluate the interaction and regulation of endogenous corticosteroids with immune cells in vivo in the domestic pig. Functional measures of immune suppression suggest that the pig is relatively resistant to DEX. Furthermore, type II corticosteroid receptors exclusively bind DEX with high affinity, whereas type I receptors, the so-called mineralocorticoid receptors, have a higher affinity for cortisol. In addition, DEX is not bound by serum binding proteins as are endogenous corticosteroids. These issues prompted us to revisit glucocorticoid regulation of type 1 and type 2 cytokines in cultured pig splenocytes and to test the broad hypothesis that cortisol biases cytokine production in favor of a Th2 response. We evaluated interferon gamma (IFNgamma) (also interleukin 2 (IL-2) in one experiment) and interleukin 10 (IL-10) as representative Th1 and Th2 cytokines, respectively. Furthermore, we evaluated macrophage migration inhibitory factor (MIF) because it is reported to be an essential factor in T cell activation; it is also upregulated by glucocorticoids and reported to be a product of Th2 lymphocytes. In general, both IFNgamma and IL-10 were sensitive to cortisol inhibition early in culture. However, IFNgamma ultimately escaped cortisol inhibition, whereas IL-10 continued to be substantially suppressed by high physiological concentrations of cortisol. Similarly, MIF mRNA could be suppressed by cortisol, but only when cortisol was added to cultures after ConA (concanavalin A) stimulation of splenocytes. So, taken together, our studies do not support the hypothesis that cortisol favors a Th2 cytokine profile in cultured pig splenocytes.
Skjolaas
K A
KA
Department of Animal Sciences and Industry, Kansas State University, 253 Weber Hall, Manhattan, KS 66506-0201, USA.
Minton
J E
JE
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005938:Glucocorticoids / Q000494:pharmacology; D006854:Hydrocortisone / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology*; D013552:Swine / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D006854:Hydrocortisone