Am. J. Respir. Cell Mol. Biol., Vol 11, No. 4, Oct 1994, 473-479.
Interleukin-1 receptor antagonist protein inhibits the synthesis of IgE and proinflammatory cytokines by allergen-stimulated mononuclear cells
TC Sim, KA Hilsmeier, LM Reece, JA Grant and R Alam
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0762.
The ability of interleukin-1 (IL-1) to activate diverse cell populations
supports its role as a preeminent cytokine in the pathogenesis of chronic
inflammation. In this study, we investigated the role of Il-1 and IL-1
receptor antagonist protein (IRAP) in the regulation of allergen-induced
synthesis of IgE and proinflammatory cytokines. The temporal expression of
IL-1 beta and IRAP during 5-day allergen-activated peripheral mononuclear
cell (PMNC) cultures suggested differential production of the two
cytokines. To determine the influence of IRAP on IL-1-mediated cellular
responses, we cultured PMNC from allergic donors with specific allergens in
the presence or absence of IRAP pretreatment. Culture supernatants were
assayed for IgE and cytokines using specific enzyme-linked immunosorbent
assay. IRAP at concentrations 0.01, 0.1, and 1 microgram/ml decreased the
allergen- stimulated IgE synthesis by 33 +/- 7%, 50 +/- 7%, and 66 +/- 5%,
respectively (P < 0.05). Increasing the concentration of allergen did
not affect the reduction in IgE synthesis observed in the presence of IRAP.
Lipopolysaccharide-stimulated IgE synthesis was also significantly
inhibited by IRAP (P < 0.05). In parallel experiments, anti-IL-1 beta
monoclonal antibody showed a comparable inhibitory pattern on IgE synthesis
(P < 0.05). IRAP inhibited the synthesis of interleukin-6, tumor
necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor
in a dose-dependent manner (P < 0.05); the mean inhibition was 31 +/-
4%, 75 +/- 5%, and 88 +/- 2%, respectively, at 1 microgram/ml of
IRAP.(ABSTRACT TRUNCATED AT 250 WORDS)
