Interleukin-1 receptor antagonist protein inhibits the synthesis of IgE and proinflammatory cytokines by allergen-stimulated mononuclear cells.

T. C. Sim, K. A. Hilsmeier, L. M. Reece, J. A. Grant, R. Alam

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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)

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Issue number4
StatePublished - Oct 1994


ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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