Regulatory effects of endogenous interleukin-1 receptor antagonist protein in immunoglobulin G immune complex-induced lung injury

Thomas P. Shanley, James L. Peters, Michael L. Jones, Stephen W. Chensue, Steven L. Kunkel, Peter A. Ward*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

IL-1 receptor antagonist (IL-1Ra) has regulatory effects on IL-1 activity both in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered human IL-1Ra suppressed neutrophil recruitment and ensuing lung injury. In this study, we sought to determine if endogenous rat IL-1Ra might regulate this lung-inflammatory response. By Northern blot analysis of lung mRNA and Western analysis of bronchoalveolar lavage (BAL) fluids, rat IL-1Ra expression was found to increase during development of inflammation in IgG immune complex-mediated alveolitis. By immunostaining, alveolar macrophages and recruited neutrophils were the apparent sources of IL-1Ra. In vivo blocking of endogenous IL-1Ra resulted in a 53% increase in lung vascular permeability and a 180% increase in BAL fluid neutrophils. In companion studies, a significant increase in BAL IL-1β was found, whereas no significant change in TNF-α activity was observed. Whereas the in vivo regulatory effects of IL-1Ra appear to be limited to IL-1β, IL-10 regulates both IL-1β and TNF-α in this model, reflected by a 48% increase in BAL IL- 1β in rats treated with anti-IL-10. These findings suggest that IL-1Ra is an intrinsic regulator of inflammatory injury after deposition of IgG immune complexes and that it regulates production of IL-1β.

Original languageEnglish (US)
Pages (from-to)963-970
Number of pages8
JournalJournal of Clinical Investigation
Volume97
Issue number4
DOIs
StatePublished - Feb 15 1996

Keywords

  • IL-1Ra
  • IL-1β
  • TNF-α
  • immune complexes
  • lung injury
  • neutrophils

ASJC Scopus subject areas

  • Medicine(all)

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