IL-12 directs severe renal injury, crescent formation and Th1 responses in murine glomerulonephritis.

Abstract:

:Glomerular crescent formation characterizes severe glomerulonephritis (GN). Evidence suggests that crescent formation results from a delayed-type hypersensitivity-like Th1 response. As IL-12 directs Th1 responses, we tested the hypothesis that IL-12 is important in crescentic GN. Neutralization of IL-12 attenuated crescent formation and cell-mediated injury in C57BL/6 mice sensitized to and challenged with sheep anti-mouse glomerular basement membrane (GBM) globulin. Recombinant IL-12 induced severe crescentic GN with enhanced Th1 responses in C57BL/6 mice in which non-crescentic GN was induced by injecting anti-GBM globulin into naive mice. BALB/c mice do not develop significant crescent formation in these models, due either to regulatory effects of IL-4, or to deficits in IL-12 production/responsiveness. Administering IL-12 to BALB/c mice with GN induced Th1 responses and crescent formation, whereas IL-4-deficient BALB/c mice did not develop cell-mediated crescentic injury when GN was induced in sensitized mice. These results establish a central role for IL-12 in severe crescentic GN.

journal_name

Eur J Immunol

authors

Kitching AR,Tipping PG,Holdsworth SR

doi

10.1002/(SICI)1521-4141(199901)29:01<1::AID-IMMU1>

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

1-10

issue

1

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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