Differential expression of various cytokine and chemokine genes between proliferative and non-proliferative glomerulonephritides

Background: Intraglomerular Cellular proliferation is one of the major dete rminants for dividing various glomerulonephritis (GN) into two groups, such as proliferative versus non-proliferative. Cytokines and chemokines are in volved in the pathogenetic pathways and would affect the functional and his tologic sequelae. We hypothesized that the morphological difference might b e based on the differential intrarenal expression of various cytokines and chemokines. We quantified the intrarenal gene expression of various cytokin es and chemokines, and correlated it with clinical parameters. Methods: Tot al RNA was extracted from 54 proliferative GN (PGN) core biopsy specimens a nd 42 non-proliferative GN (NPGN) specimens. Using the internal competitors , RT-PCR was instituted to quantify mRNAs. Results: The magnitude of the ge ne expressions of IL-2, IFN-gamma, and IFN-gamma /IL-10 ratio were signific antly higher in PGN than in NPGN. RANTES and IL-8 had more abundant gene me ssages in PGN. It was shown that Th1 cytokine was upregulated if GN was med iated by immune complexes regardless of cellular proliferation. But chemoki nes had the elevated levels of expression in PGN among immune complex-media ted GN. Upregulation of the IFN-gamma /IL-10 ratio and TNF-alpha was associ ated with poor renal function at the time of biopsy. Renal tissues from the patients with a non-nephrotic range of proteinuria showed abundant message s for proinflammatory cytokines and chemokines. Conclusion: Th1, proinflamm atory cytokines, and chemokines were more abundant in proliferative GN, and correlated with unfavorable clinical parameters. We propose that the clini cal manifestations and diverse histologic features of human GN are associat ed with differential expressions of specific cytokines and chemokines.