Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.

T Wada, N Tomosugi, T Naito, H Yokoyama… - The Journal of …, 1994 - rupress.org
T Wada, N Tomosugi, T Naito, H Yokoyama, K Kobayashi, A Harada, N Mukaida…
The Journal of experimental medicine, 1994rupress.org
Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The
pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine
(chemokine), was explored in an animal model of acute immune complex-mediated
glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection
of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes
consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but …
Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli 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 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.
rupress.org