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 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)-alpha 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-alpha 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-alpha 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-alpha production.
Shanley
T P
TP
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Foreback
J L
JL
Remick
D G
DG
Ulich
T R
TR
Kunkel
S L
SL
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002469:Cell Separation; D007105:Immune Complex Diseases / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G / Q000633:toxicity*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha