Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.
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.
Wada
T
T
First Department of Internal Medicine, School of Medicine, Kanazawa University, Ishikawa, Japan.
Tomosugi
N
N
Naito
T
T
Yokoyama
H
H
Kobayashi
K
K
Harada
A
A
Mukaida
N
N
Matsushima
K
K
D000208:Acute Disease; D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D005921:Glomerulonephritis / Q000473:pathology / Q000628:therapy*; D016209:Interleukin-8 / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D011507:Proteinuria / Q000517:prevention & control*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D016209:Interleukin-8