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 to investigate the immediate actions of the proinflammatory cytokines IL-1β, TNF-α, and 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 anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously 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 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 (51Cr-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 (Ficoll50-80Å), 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 in the GFB.
Department of Nephrology, Lund University, Lund, Sweden.
Kristinn
K
Sverrisson
Department of Nephrology, Lund University, Lund, Sweden.
Josefin
J
Axelsson
Department of Nephrology, Lund University, Lund, Sweden.
Anna
A
Rippe
Department of Nephrology, Lund University, Lund, Sweden.
Daniel
D
Asgeirsson
Department of Nephrology, Lund University, Lund, Sweden Bengt.Rippe@med.lu.se.
Bengt
B
Rippe
D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002850:Chromatography, Gel; D016166:Free Radical Scavengers / Q000494:pharmacology; D060730:Glomerular Filtration Barrier / Q000187:drug effects* / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D010539:Permeability; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D016166:Free Radical Scavengers; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha
Ficoll; cytokines; glomerular permeability; sepsis; tempol