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| Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: Clinical implications |
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| Author(s): Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP |
| Source: PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS Volume: 108 Issue: 5 Pages: 374-381 Published: SEP 1996 |
| Times Cited: 237 References: 36 |
| Abstract: 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-effecters 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA
2. NIAMS, ARTHRIT & RHEUMATISM BRANCH, NIH, BETHESDA, MD USA |
| Publisher: BLACKWELL SCIENCE INC, 238 MAIN ST, CAMBRIDGE, MA 02142 |
| Subject Category: Medicine, General & Internal; Medicine, Research & Experimental |
| IDS Number: VP845 |
| ISSN: 1081-650X |
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