IL-4 IS AN ENDOGENOUS INHIBITOR OF NEUTROPHIL INFLUX AND SUBSEQUENT PATHOLOGY IN ACUTE ANTIBODY-MEDIATED INFLAMMATION

IL-4 is an immunoregulatory cytokine that has in vitro and in vivo ant i-inflammatory actions. In this study we investigated whether endogeno usly produced IL-4 modulates inflammatory processes that occur after A bs bind to target tissue by comparing the severity of glomerulonephrit is induced by heterologous anti-glomerular basement membrane Abs in wi ld-type (IL-4(+/+)) mice to that of glomerulonephritis induced in homo zygous IL-4 gene knockout (IL-4(-/-)) mice. Two hours after Ab injecti on, IL-4(-/-)mice had significantly higher intrarenal intercellular ad hesion molecule-1 mRNA expression and intraglomerular neutrophil accum ulation than the IL-4(+/+) group. Treatment of IL-4(-/-)mice with reco mbinant murine IL-4 at the time of disease induction reduced intercell ular adhesion molecule-1 expression and neutrophil influx to levels ob served in IL-4(+/+) kidneys. Four days after Ab administration, untrea ted IL-4(-/-)mice developed significantly greater urinary protein excr etion, intracapillary fibrinogen deposits, and glomerular hypercellula rity than IL-4(+/+) mice. These results demonstrate that endogenous IL -4 suppresses neutrophil influx and limits tissue damage in Ah-induced glomerulonephritis, suggesting that IL-4 is an important regulator of acute inflammatory processes.