title: Unilateral renal ischaemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased capillary permeability.
abstract: A better understanding of the inflammatory process associated with renal ischaemia-reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and returned to control levels after 120 min reperfusion. The responses were differentiated; interleukin-1β, monocyte chemoattractant protein-1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischaemic kidney. Tumour necrosis factor-α was the only mediator showing elevated lymph-to-plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR-induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14- to 166-fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischaemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph.
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.
authors.forename: Liliana Monica
authors.initials: LM
authors.lastname: Bivol
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.|Haukeland University Hospital, Norway.
authors.forename: Bjarne Magnus
authors.initials: BM
authors.lastname: Iversen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.|Haukeland University Hospital, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Hultström
authors.affiliation: Department of Biomedicine, University of Bergen, Norway.
authors.forename: Paal William
authors.initials: PW
authors.lastname: Wallace
authors.affiliation: Department of Biomedicine, University of Bergen, Norway.|Centre for Cancer Biomarkers (CCBIO), University of Bergen, Norway.
authors.forename: Rolf Kåre
authors.initials: RK
authors.lastname: Reed
authors.affiliation: Department of Biomedicine, University of Bergen, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Wiig
authors.affiliation: Department of Biomedicine, University of Bergen, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Tenstad
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008196:Lymph / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation
chemical_list: D016207:Cytokines