The process of glomerular injury in nephrotoxic serum nephritis (NTN) is dependent on proinflammatory cytokines. In the present investigation, we assessed the actions of neutralizing antibody against IL-1 beta, TNF-alpha, IL-6 and TGF-beta 1 on glomerular injury. Marked increase in IL-1 beta and IL-6 was detected in cultured glomeruli of NTN in mice throughout the experiments from disease induction. Protein of TNF-alpha and TGF-beta 1 also increased in NTN mice 1 day after disease induction. Treatment with either IL-1 beta or TNF-alpha neutralizing antibody reduced proteinuria from 71 +/- 11.2 m g/24 hr to 32.2 +/- 6.0 (P < 0.01). 34.3 +/- 6.8 mg/24 hr (P < 0.01), respectively. Although the effect of IL-6 neutralizing antibody on proteinuria was not remarkable, the decreased creatinine clearance was improved more than that of IL-1 beta or TNF-alpha. Antibody against TGF-beta 1 had no effect on proteinuria and creatinine clearance. Treatments with IL-1 beta, TNF-alpha and IL-6 neutralizing antibodies inhibited glomerular hypercellularity in NTN mice. TGF-beta 1 neutralizing antibody suppressed the index of mesangial matrix expansion. IL-1 beta and TNF-alpha neutralizing antibodies prevented the increase in the number of macrophages in the glomeruli. The number of PCNA positive cells and alpha-smooth muscle actin expression in glomeruli was significantly reduced in the IL-6 neutralizing antibody-treated group. These results confirm the direct involvement of IL-1 beta, TNF-alpha and IL-6 in mouse NTN. We speculate that TGF-beta 1 may inhibit excessive proliferation in glomerular cells.