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

J Clin Invest. 1996 Feb 15;97(4):963-70. doi: 10.1172/JCI118520.


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 IL-1beta was found, whereas no significant change in TNF-alpha activity was observed. Whereas the in vivo regulatory effects of IL-1R appear to be limited to IL-1beta, IL-10 regulates both IL-1beta and TNF-alpha in this model, reflected by a 48% increase in BAL IL-1beta 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-1beta.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alveolitis, Extrinsic Allergic / physiopathology*
  • Animals
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / immunology
  • DNA Primers / chemistry
  • Gene Expression
  • Immune Complex Diseases / physiopathology*
  • Immunoglobulin G / immunology
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / physiology*
  • Male
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Rats
  • Sialoglycoproteins / physiology*
  • Tumor Necrosis Factor-alpha / metabolism


  • DNA Primers
  • IL1RN protein, human
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • RNA, Messenger
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha