Regulatory effects of interleukin-6 in immunoglobulin G immune-complex- induced lung injury

Thomas P. Shanley, Jami L. Foreback, Daniel G. Remick, Thomas R. Ulich, Steven L. Kunkel, Peter A. Ward*

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Interleukin-6 (IL-6) is a cytokine produced in response to a variety of inflammatory stimuli. Although IL-6 is often observed in increased amounts in acute respiratory distress syndrome, its role in the development 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 analysis and bioactivity, was found as a function of time during the course of development of injury. Recombinant IL-6 instilled intratracheally at commencement of injury led to substantial reductions in lung vascular permeability, neutrophil accumulation, and levels of tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 in bronchoalveolar lavage fluids. Conversely, blocking of intrinsic IL-6 by a neutralizing antibody resulted in increases in lung vascular permeability, neutrophil content, and TNF-α levels in bronchoalveolar lavage fluids. Rat alveolar macrophages stimulated in vitro with lipopolysaccharide in the presence of IL-6 showed a significant reduction in TNF-α expression. Together, these findings suggest that IL-6 acts as an intrinsic regulator of lung inflammatory injury after deposition of IgG immune complexes and that the protective effects of exogenously administered IL-6 may be in part linked to suppressed TNF-α production.

Original languageEnglish (US)
Pages (from-to)193-203
Number of pages11
JournalAmerican Journal of Pathology
Volume151
Issue number1
StatePublished - 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Shanley, T. P., Foreback, J. L., Remick, D. G., Ulich, T. R., Kunkel, S. L., & Ward, P. A. (1997). Regulatory effects of interleukin-6 in immunoglobulin G immune-complex- induced lung injury. American Journal of Pathology, 151(1), 193-203.