Renal cytokine profile in an endotoxemic porcine model

Abstract

In animals exposed to acute endotoxemia with lipopolysaccharide (LPS), high levels of cytokines are found in the kidney. The objective of this study is to determine whether the high renal content of TNF-alpha, IL-1beta, IL-10 and IL-1 receptor antagonist (IL-1ra) is due to glomerular filtration and reabsorption, or whether the cytokines are produced locally in the kidney. Eighteen anesthetized and mechanically ventilated pigs (35-43 kg) were randomized into two groups: Group 1 (n=12) LPS infusion for 360 min and Group 2 (n=6) control pigs, no treatment. At 360 min, the pigs were euthanized and tissue samples from the kidneys were obtained. Localization of the cytokines was determined by immunohistochemistry and double immunofluorescence (dIF). Pigs exposed to endotoxemia showed increased accumulation of leukocytes and increased protein expression of TNF-alpha and IL-1beta when compared with controls. dIF showed that TNF-alpha-positive cells co-localized with both endothelial and mesangial cells in the glomeruli. Furthermore, the endothelial cells of the cortical arterioles were positive for IL-1beta. TNF-alpha and IL-1beta staining were absent in renal tubular cells. A positive signal for IL-10 was detected at the tubular brush border while IL-1ra was detected in the glomerulus and in the tubular cells. LPS-induced endotoxemia increased TNF-alpha and IL-1beta protein expression and leukocyte accumulation in the kidneys. The results indicate that the increased levels of the pro-inflammatory cytokines TNF-alpha and IL-1beta are caused by a local production in the kidneys while the anti-inflammatory cytokines IL-10 and IL-1ra are filtrated and reabsorbed in the tubuli.