Effects of a Corticosteroid, Budesonide, on Production of Bioactive Il-12 by Human Monocytes

ISSN： 1043-4666

Source： Cytokine, Vol.10, Iss.10, 1998-10, pp. : 786-789

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Abstract

Interleukin 12 (IL-12) has a key role during the initial phase of the immune response, favouring development of T helper class 1 (Th1) cells. IL-12 is composed of two subunits, p35 and p40, which are both needed for bioactivity. The level of p35 expression determines the level of bioactive IL-12 (p70), while the p40 subunit is produced in excess. In the present study we examined the sensitivity of bioactive IL-12 production by human monocytes to a corticosteroid, budesonide. We also compared the corticosteroid sensitivity of IL-12 and two other cytokines, interleukin 1&bgr; and granulocyte–macrophage colony-stimulating factor (GM-CSF). Monocytes obtained from peripheral blood of healthy donors (n=12) were stimulated with lipopolysaccharide (LPS; 10 μg/ml; 20 h) in the presence or absence of budesonide (10^-11–10^-7 M). The supernatants were assayed for IL-12 (p70), IL-1&bgr; and GM-CSF concentrations using specific immunoassays. Budesonide potently inhibited the production of bioactive IL-12. A significant suppression was obtained by treatment with even very low budesonide concentrations; even 10^-11 M budesonide significantly inhibited IL-12 to 81.6±7.6% of the control level (P<0.05). The maximal inhibitory effect of budesonide was seen at 10^-8 M. The inhibition of IL-12 production was significantly higher than the inhibition of GM-CSF (P<0.01) or IL-1&bgr; (P<0.001). Whereas IL-12 production was totally inhibited, GM-CSF production was inhibited to 16.4±3.7 and IL-1&bgr; production to 43.1±7.3% of control, respectively. The dramatic capacity of corticosteroids to modulate production of IL-12 as well as other cytokines may be a major mechanism underlying the effectiveness of these drugs in a broad spectrum of inflammatory diseases.