• Corpus ID: 22109868

Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications.

@article{Elenkov1996ModulatoryEO,
  title={Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications.},
  author={Ilia J. Elenkov and Dimitris A. Papanicolaou and Ronald L. Wilder and George P. Chrousos},
  journal={Proceedings of the Association of American Physicians},
  year={1996},
  volume={108 5},
  pages={
          374-81
        }
}

• I. Elenkov, D. Papanicolaou, +1 author G. Chrousos
• Published 1 September 1996
• Biology, Medicine
• Proceedings of the Association of American Physicians

Interleukin-12 (IL-12) is a key inducer of differentiation of uncommitted T helper (TH) cells toward the TH1 phenotype, which regulates cellular immunity, whereas IL-10 inhibits TH1 functions and potentiates TH2-regulated responses (i.e., humoral immunity). To examine the potential effects of stress on TH1/TH2 balance, we studied the ability of three prototype stress hormones-dexamethasone (a synthetic glucocorticoid) and the catecholamines norepinephrine and epinephrine-to alter the production of IL-12 (p70) and IL-10 induced by bacterial lipopolysaccharide (LPS) in human whole blood. Dexamethasone inhibited LPS-induced bioactive IL-12 production in a dose-dependent fashion and at physiologically relevant concentrations; it had no effect on IL-10 secretion. The glucocorticoid-induced reduction of IL-12 production was antagonized by RU 486, a glucocorticoid-receptor antagonist, suggesting that it was mediated by the glucocorticoid receptor. Norepinephrine and epinephrine also suppressed IL-12 production in a dose-dependent fashion and at physiological concentrations; both catecholamines, however, dose-dependently increased the production of IL-10. The effects of either catecholamine on IL-12 or IL-10 secretion were blocked completely by propranolol, a beta-adrenoreceptor antagonist, indicating that they were mediated by the beta-adrenergic receptor. These findings suggest that the central nervous system may regulate IL-12 and IL-10 secretion and, hence, TH1/TH2 balance via the peripheral end-effectors of the stress system. Thus, stress may cause a selective suppression of TH1 functions and a shift toward a TH2 cytokine pattern rather than generalized TH suppression. The TH1-to-TH2 shift may be responsible for the stress-induced susceptibility of the organism to certain infections. Through the same or a reciprocal mechanism, states associated with chronic hyperactivity or hypoactivity of the stress system might influence the susceptibility of an individual to certain autoimmune, allergic, infectious, or neoplastic diseases.