PREVENTION OF PROTEINURIA BY THE ADMINISTRATION OF ANTI-INTERLEUKIN-8ANTIBODY IN EXPERIMENTAL ACUTE IMMUNE COMPLEX-INDUCED GLOMERULONEPHRITIS

Glomerular infiltration by neutrophils is a hallmark of acute glomerul onephritis. The pathophysiological role of interleukin 8 (IL-8), a pot ent neutrophil chemotactic cytokine (chemokine), was explored in an an imal model of acute immune complex-mediated glomerulonephritis by admi nistering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immun e complexes consisting of BSA and rabbit IgG in glomeruli. Histologica l analyses revealed a small but significant number of neutrophils in g lomeruli and the fusion of epithelial cell foot processes. Concomitant ly, urinary levels of protein and albumin increased markedly(3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untr eated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). An ti-IL-8 antibody treatment decreased the number of neutrophils in glom eruli by 40% and dramatically prevented the fusion of epithelial cell foot process Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 a nd 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL- 8 participated in the impairment of renal functions in experimental ac ute immune complex-mediated glomerulonephritis through activating as w ell as recruiting neutrophils.