Effect of steroid and cyclophosphamide pulse therapy on glomerular chemokine expression in patients with crescentic glomerulonephritis

Objective:To study the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α and β (MIP-1α, MIP-1β), in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. Methodology:Twelve patients with initial biopsy proven CGN(immune complex mediated CGN,type Ⅱ CGN in 6 patients and pauci--immune CGN,type Ⅲ CGN in another 6 patients)were enrolled in this study,they undertook an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and repeat biopsy one to three months later.The expressions of MCP-1,MIP-1α,MIP-1β,and CD68 in glomeruli with cellular crescents and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies.The effect of the pulse therapy on histopathological changes was also observed. Results:Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescentic formation both in type Ⅱ CGN and type Ⅲ CGN,the effect of the therapy on glomerular chemokine expression was quite different between type Ⅱ CGN and type Ⅲ CGN.It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68,MCP-1,and MIP-1α,but had no effect on MIP-1β in glomeruli with cellular crescents of patients with type Ⅱ CGN.In patients with type Ⅲ CGN,the therapy also reduced the expression of CD68,but had no effect on MCP-1,MIP-1α,and MIP-1β in glomeruli with cellular crescents.It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in type Ⅲ CGN as compared with that of type Ⅱ CGN. Conclusion:The different responseto steroid and CTX intermittent intravenous pulse therapy found in type Ⅱ CGN and type Ⅲ CGN may correlate with the different changes of the expression of MCP-1 and MIP-1α in the glomeruli of patients with type Ⅱ CGN and type Ⅲ CGN after the treatment.