title: Anti-TNF-α Agent Infliximab and Splenectomy Are Protective Against Renal Ischemia-Reperfusion Injury.
abstract: BACKGROUND
  Renal ischemia-reperfusion (I/R) injury is associated with delayed graft function and results in poor long-term graft survival. We previously showed that splenectomy (SPLN) protects the kidney from I/R injury and reduces serum TNF-α levels. Herein, we further investigated the effects of SPLN on inflammatory responses and tissue injury in renal I/R by examining the expression of major inflammatory cytokines and heat shock protein 70 (HSP70). Because it was shown previously that the anti-TNF-α agent infliximab (IFX) attenuated renal I/R injury, we also investigated whether IFX administration mimics the effects of SPLN.
  
  
  METHODS
  The left renal pedicles of adult male Wistar rats were clamped for 45 minutes and then reperfused for 24 hours; right nephrectomy and SPLN were performed immediately. A separate cohort was administered IFX 1 hour before surgery in lieu of SPLN.
  
  
  RESULTS
  Serum creatinine and blood urea nitrogen levels were markedly elevated by I/R injury; these increases were significantly reversed by IFX. Furthermore, IFX inhibited the induction of inflammatory cytokines and HSP70 during renal I/R injury. Time-dependent profiles revealed that the expression of inflammatory cytokines was elevated immediately after I/R, whereas levels of HSP70, serum creatinine, and blood urea nitrogen began to rise 3 hours postreperfusion. Macrophages/monocytes were significantly increased in I/R-injured kidneys, but not in those administered IFX. The outcomes of SPLN mirrored those of IFX administration.
  
  
  CONCLUSIONS
  Splenectomy and TNF-α inhibition both protect the kidney from I/R injury by reducing the accumulation of renal macrophages/monocytes and induction of major inflammatory cytokines.
authors.affiliation: 1 Department of Urology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.2 Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Nagata
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Naohito
authors.initials: N
authors.lastname: Isoyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsumura
authors.forename: Koki
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Eiichi
authors.initials: E
authors.lastname: Takaki
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takii
authors.forename: Akira
authors.initials: A
authors.lastname: Nakai
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D000069285:Infliximab / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013156:Splenectomy; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D000069285:Infliximab