Antiserum against tumor necrosis factor-alpha and a protease inhibitor reduce immune glomerular injury View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1991-07

AUTHORS

Zbigniew W. Hruby, Kinji Shirota, Serge Jothy, Robin P. Lowry

ABSTRACT

Previous studies in this laboratory have documented tumor necrosis factor alpha (TNF) release by macrophage laden glomeruli in the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN). We now report that the administration of anti-TNF antiserum to rats with the AA-NTSN reduces albuminuria in a dose related manner (day 8 postinduction) and limits glomerular necrosis (P less than 0.05) without affecting the endogenous creatinine clearance (CCr). Protease inhibitors block cytolytic activity of TNF in vitro and reduce glomerular necrosis in experimental nephritis in vivo. The combined administration of anti-TNF antiserum and an amidine-type protease inhibitor (BABIM) to rats with the AA-NTSN caused a greater diminution of albuminuria and histopathology than observed in rats treated with either agent alone, and also prevented the fall in CCr otherwise observed in this model system. Since, in our studies, BABIM did not inhibit cytolytic TNF activity in vitro, we conclude that the effects of combined administration of these two agents are mediated by independent mechanisms. Our results highlight the pathogenic significance of local TNF release in immune renal disease accompanied by prominent glomerular macrophage accumulation. More... »

PAGES

43-51

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ki.1991.177

DOI

http://dx.doi.org/10.1038/ki.1991.177

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007808437

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1921154


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