Crescentic glomerulonephritis - a manifestation of a nephritogenic Th1 response?

Crescentic glomerulonephritis (GN) is the histopathological correlate of th e clinical syndrome of rapidly progressive glomerulonephritis. Glomerular c rescent formation complicates proliferative forms of GN and indicates sever e disease with a poor renal prognosis. In the past 10 years evidence from e xperimental models of GN and from human disease has accumulated suggesting that crescentic glomerulonephritis is a manifestation of a delayed type hyp ersensitivity (DTH)-like response to nephritogenic antigens. The elucidatio n of T helper 1 (Th1) and Th2 subsets in mice and in humans has led to the hypothesis that crescentic GN is a manifestation of a Th1 predominant DTH m ediated immune response. Recent experiments performed mainly in a murine mo del of crescentic glomerulonephritis have tested this hypothesis. Crescent formation in this model is substantially interleukin (IL)-12 and interferon -gamma (IFN-gamma) dependent. Administration of IL-12, deletion of endogeno us IL-4 or IL-10 results in enhanced disease, while administration of exoge nous IL-4 and/or IL-10 reduces crescentic injury. These findings, together with the available evidence from human studies (examining the pattern of im mune effecters in glomeruli, data on cytokine production by peripheral bloo d mononuclear cells and case reports of the induction of proliferative and/ or crescentic GN by administration of IFN-gamma or IL-2) suggest that human crescentic GN is manifestation of a Th1 mediated DTH-like nephritogenic im mune response.