Premium
Renal cytokine profile in an endotoxemic porcine model
Author(s) -
GRANFELDT A.,
EBDRUP L.,
TØNNESEN E.,
WOGENSEN L.
Publication year - 2008
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2008.01625.x
Subject(s) - medicine , cytokine , tumor necrosis factor alpha , lipopolysaccharide , kidney , reabsorption , endocrinology , alpha (finance) , receptor , receptor antagonist , immunohistochemistry , inflammation , antagonist , construct validity , nursing , patient satisfaction
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‐α, IL‐1β, 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. Methods: 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). Results: Pigs exposed to endotoxemia showed increased accumulation of leukocytes and increased protein expression of TNF‐α and IL‐1β when compared with controls. dIF showed that TNF‐α‐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‐1β. TNF‐α and IL‐1β 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. Conclusion: LPS‐induced endotoxemia increased TNF‐α and IL‐1β protein expression and leukocyte accumulation in the kidneys. The results indicate that the increased levels of the pro‐inflammatory cytokines TNF‐α and IL‐1β 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.