Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo

This study was performed in order to investigate the immediate actions of the proinflammatory cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anaesthetized rats blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused i.v. with either IL-1β (0.4 and 2 μg·kg(-1)·h(-1)), TNF-α (0.4 and 2 μg·kg(-1)·h(-1)) or IL-6 (4 and 8 μg·kg(-1)·h(-1)), together with polydisperse fluorescein isothiocyanate (FITC)-Ficoll-70/400 and Inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (θ). The glomerular filtration rate (GFR) was also assessed ((51)Cr-EDTA). In separate experiments the superoxide scavenger, tempol (30 mg·kg(-1)·h(-1)), was given before and during cytokine infusions. IL-1β and TNF-α caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll50-80A), peaking at 5-30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1β, TNF-α and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger, tempol, suggesting an important role of ROS in acute cytokine induced permeability changes of the GFB. (Less)