IL-1 and TNF independent pathways mediate ICAM-1/VCAM-1 up-regulation in ischemia reperfusion injury

In vitro studies have suggested that targeting interleukin (IL)-1 and tumor necrosis factor (TNF) can be used to regulate intercellular adhesion molec ule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and potential ly treat kidney inflammation. We therefore evaluated ICAM-1 and VCAM-1 regu lation in knockout (KO) mice deficient in both IL-1 receptor 1 (R1) and TNF -R1 during renal ischemia reperfusion injury. ICAM-1 and VCAM-1 mRNA expres sion was measured with specific murine probes and Northern blotting (n=4/gr oup). Protein expression was measured using immunohistochemistry. Serum cre atinine (SCr), tubular histology, and neutrophil infiltration into postisch emic kidneys were also quantified. ICAM-1 and VCAM-1 mRNA expression increa sed in both wild-type (WT) and KO mice at 2, 6, and 24 h. Protein expressio n of ICAM-1 and VCAM-1 was also increased at 24 It postischemia. SCr levels and tubular necrosis scores were comparable in WT and KO mice at 24 and 48 h. Neutrophil migration in KO mice was decreased at 24 It but comparable t o WT at 48 h. These data demonstrate that IL-1 and TNF are not essential fo r postischemic increases in ICAM-1 and VCAM-1.