Effect of interleukin-8 on glomerular sulfated compounds and albuminuria

To evaluate the effect of interleukin-8 (IL8) on glomerular basement membrane (GBM) sulfated compounds and albuminuria, we infused IL8 in 1% bovine serum albumin (BSA) for 5 days into the left renal artery of Holtzman male rats at the rate of 10 microliters/h using an osmotic pump. Control rats received 1% BSA. A significant increase in urinary albumin/creatinine ratio was seen on the last day of IL8 infusion (0.38 +/- 0.11, mean +/- SEM) when compared with albumin/creatinine ratio prior to infusion (0.19 +/- 0.04, P = 0.04). No significant differences in urinary albumin excretion prior to and after infusion of 1% BSA were observed. On the last day of infusion, rats were injected with 35sulfate (1.0 mCi/200 g body weight) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. After 5 days of IL8 administration, there was a significant increase in 35sulfate uptake by GBM of the infused kidney (76 +/- 10 cpm/dry glomerular weight, mean +/- SEM) compared with the uptake seen in the contralateral kidney (53 +/- 9, P = 0.05). The in vivo infusion of IL8 increased the 35sulfate uptake by GBM and augmented the urinary albumin/creatinine ratio, suggesting that IL8 may induce albuminuria by altering the metabolism of the GBM sulfated compounds. This hypothesis needs to be confirmed by studies on glomerular charge selectivity and GBM anionic sites during the course of the infusion. Moreover, the persistence of the effect needs to be evaluated by prolonging the infusion for more than 5 days.