PT  - JOURNAL ARTICLE
AU  - TIMOSHANKO, JENNIFER R.
AU  - KITCHING, A. RICHARD
AU  - HOLDSWORTH, STEPHEN R.
AU  - TIPPING, PETER G.
TI  - Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis
DP  - 2001 Mar 01
TA  - Journal of the American Society of Nephrology
PG  - 464--471
VI  - 12
IP  - 3
4099  - http://jasn.asnjournals.org/content/12/3/464.short
4100  - http://jasn.asnjournals.org/content/12/3/464.full
SO  - J. Am. Soc. Nephrol.2001 Mar 01; 12
AB  - Abstract. Interleukin-12 (IL-12) directs the cognate nephritogenic T helper type 1 responses that initiate renal injury in murine crescentic glomerulonephritis (GN). The recent demonstration of IL-12 production by intrinsic renal cells, including mesangial and proximal tubular cells, raises the possibility that IL-12 from nonimmune cells may contribute to inflammatory renal injury. To address this possibility, the development of sheep anti-mouse glomerular basement membrane globulin—induced crescentic GN was studied in C57BL/6 wild-type (WT), IL-12—deficient (IL-12 -/-), and IL-12 “chimeric” mice. IL-12 chimeric mice were produced by transplantation of WT bone marrow into IL-12 -/- mice to restore IL-12 production by immune cells, while leaving them deficient in renal IL-12 production. WT and “sham” chimeric mice (normal bone marrow transplanted into WT mice) developed crescentic GN with glomerular T-cell and macrophage recruitment and impaired renal function (elevated proteinuria and serum creatinine) 10 d after initiation of GN. IL-12 -/- mice showed significant protection from GN. Chimeric IL-12 mice showed significant attenuation of crescent formation, glomerular T-cell and macrophage accumulation, and renal impairment, compared with WT and sham chimeric mice, but were not protected to the same extent as IL-12 -/- mice. IL-12 chimeric mice showed no attenuation of their systemic cognate immune response to the nephritogenic antigen (sheep globulin), indicated by antigen-specific circulating antibody and cutaneous delayed-type hypersensitivity. These studies indicate that IL-12 produced by non—bone marrow derived intrinsic renal cells contributes to immune renal injury. They provide the first in vivo demonstration of a proinflammatory role for an intrinsic renal cell—derived cytokine in renal inflammation.