REGULATORY EFFECTS OF INTERLEUKIN-6 IN IMMUNOGLOBULIN-G IMMUNE-COMPLEX-INDUCED LUNG INJURY

Interleukin-6 (IL-6) is a cytokine Produced in response to a variety o f inflammatory stimuli Although IL-6 is often observed in increased am ounts in acute respiratory distress syndrome, its role ill the develop ment of lung injury is unclear The role of IL-6 was studied in the rat model of lung injury induced by the intra-alveolar deposition of IgG immune complexes. IL-6 induction, as determined by Northern blot analy sis and bioactivity, was found as a function of time during the course of develoPnent of injury, Recombinant IL-6 instilled intratracheally at commencement of injury led to substantial reductions in lung vascul ar permeability, neutrophil accumulation, and levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 in bro nchoalveolar lavage fluids, Conversely, blocking of intrinsic IL-6 by a neutralizing antibody resulted ill increases iii lung vascular perme ability, neutrophil content, and TNF-alpha levels In bronchoalveolar l avage fluids, Rat alveolar macrophages stimulated in vitro with lipopo lysaccharide in the presence of IL-6 showed a significant reduction in TNF-alpha expression. Together, these findings suggest that IL-6 acts as all intrinsic regulator of lung inflammatory injury after depositi on of lgG immune complexes and that the protective effects of exogenou sly administered IL-6 may be in part linked to suppressed TNF-alpha pr oduction.