ANTI-INTERLEUKIN-8 ANTIBODY ABOLISHES EFFECTS OF LIPOID NEPHROSIS CYTOKINE

Supernatant factor from peripheral blood mononuclear cell (PBMC) cultu res of idiopathic minimal lesion nephrotic syndrome (IMLNS) patients i n relapse induces in vivo albuminuria and increases (35)sulfate uptake by glomerular basement membrane (GBM) in rats. The purpose of this st udy was to evaluate the effect of anti-interleukin 8 (IL8) neutralizin g antibody on the effects induced by the supernatant factor. Supernata nt factor col lected from six cultures of PBMC from IMLNS patients in relapse were combined and aliquoted into two samples. Anti-IL8 neutral izing antibody (750 ng) was added to one. Supernatant factor or supern atant factor and anti-IL8 antibody were infused for 5 days into the le ft renal artery of Wistar rats using an osmotic pump. On the last day of infusion, rats were injected with (35)sulfate (1.0 mCi/200 g) intra peritoneally and killed after 8 h. Glomeruli were isolated and GEM obt ained. There was a significant increase in (35)sulfate uptake of the i nfused kidney (169 +/- 52 cpm/mg dry glomerular weight, mean +/- SEM) compared with the uptake seen in the contralateral kidney (116 +/- 41, P < 0.05) when the supernatant factor was infused alone. No significa nt differences in (35)sulfate incorporation were seen between infused kidney (173 +/- 5) and contralateral kidney (190 +/- 49) when supernat ant factor and anti-IL8 antibody were administered. A significant incr ease in albuminuria was seen on the last day of infusion (0.43 +/- 0.1 1 albumin/ creatinine ratio, mean) SEM) compared with the ratio prior to infusion of the supernatant factor alone (0.18 +/- 0.03, P <0.05). No significant differences in urinary albumin/creatinine ratios prior to and on the 5th day of infusion were seen when the supernatant facto r was administered with anti-IL8 antibody. Supernatant factor effects were abolished by the addition of anti-IL8 neutralizing antibody, sugg esting that the described effects are mediated by IL8.