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

Proc Assoc Am Physicians. 1996 Sep;108(5):374-81.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Blood / metabolism*
  • Catecholamines / pharmacology*
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Epinephrine / pharmacology
  • Glucocorticoids / pharmacology*
  • Humans
  • Hypothalamo-Hypophyseal System / physiology
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mifepristone / pharmacology
  • Norepinephrine / pharmacology
  • Pituitary-Adrenal System / physiology
  • Propranolol / pharmacology
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Sympathetic Nervous System / physiology
  • T-Lymphocytes, Helper-Inducer


  • Catecholamines
  • Glucocorticoids
  • Lipopolysaccharides
  • Receptors, Glucocorticoid
  • Interleukin-10
  • Interleukin-12
  • Mifepristone
  • Dexamethasone
  • Propranolol
  • Norepinephrine
  • Epinephrine