Elsevier

Cytokine

Volume 10, Issue 10, October 1998, Pages 786-789
Cytokine

Regular article
EFFECTS OF A CORTICOSTEROID, BUDESONIDE, ON PRODUCTION OF BIOACTIVE IL-12 BY HUMAN MONOCYTES

https://doi.org/10.1006/cyto.1998.0362Get rights and content

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 1β 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 (10−11–10−7M). The supernatants were assayed for IL-12 (p70), IL-1β 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 10−11M 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 10−8M. The inhibition of IL-12 production was significantly higher than the inhibition of GM-CSF (P<0.01) or IL-1β (P<0.001). Whereas IL-12 production was totally inhibited, GM-CSF production was inhibited to 16.4±3.7 and IL-1β 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.

References (0)

Cited by (19)

  • Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor

    2007, Blood
    Citation Excerpt :

    The production of the IL-12 family is tightly controlled by a variety of modulators, and optimal induction of IL-12 requires a combination of TLR ligand stimulation plus IFN-γ. Although there are many small molecules that inhibit IL-12 production, including steroids,45,46 1,25-dihydroxyvitamin D3,47,48 acetyl salicylic acid (ASA),49 retinoids,50 thalidomide,51 and other agents which increase intracellular cAMP such as prostaglandin E2,52 β2 agonists,53 or phosphodiesterase inhibitors,54-56 most of these small-molecule IL-12 inhibitors fail to display their inhibitory activity when IL-12 production is strongly enhanced by IFN-γ. For example, pentoxifylline and thalidomide show no inhibitory activity against IFN-γ/SAC–induced IL-12 despite their significant inhibition of IL-12 induced by SAC alone.51,56

View all citing articles on Scopus
f1

Correpsondence to: Margareta Linden, Department of Cell and Molecular Biology, Astra Draco AB, Box 34, S-221 00 Lund, Sweden

View full text