PMID: 9551937Apr 29, 1998Paper

IL-4 is an endogenous inhibitor of neutrophil influx and subsequent pathology in acute antibody-mediated inflammation

The Journal of Immunology : Official Journal of the American Association of Immunologists
S SaleemF G Lakkis

Abstract

IL-4 is an immunoregulatory cytokine that has in vitro and in vivo anti-inflammatory actions. In this study we investigated whether endogenously produced IL-4 modulates inflammatory processes that occur after Abs bind to target tissue by comparing the severity of glomerulonephritis induced by heterologous anti-glomerular basement membrane Abs in wild-type (IL-4+/+) mice to that of glomerulonephritis induced in homozygous IL-4 gene knockout (IL-4-/-) mice. Two hours after Ab injection, IL-4-/- mice had significantly higher intrarenal intercellular adhesion molecule-1 mRNA expression and intraglomerular neutrophil accumulation than the IL-4+/+ group. Treatment of IL-4-/- mice with recombinant murine IL-4 at the time of disease induction reduced intercellular adhesion molecule-1 expression and neutrophil influx to levels observed in IL-4+/+ kidneys. Four days after Ab administration, untreated IL-4-/- mice developed significantly greater urinary protein excretion, intracapillary fibrinogen deposits, and glomerular hypercellularity than IL-4+/+ mice. These results demonstrate that endogenous IL-4 suppresses neutrophil influx and limits tissue damage in Ab-induced glomerulonephritis, suggesting that IL-4 is an important regulator of...Continue Reading

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