title: Isoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice.
abstract: Inflammation after renal ischemia-reperfusion (IR) injury is a major contributor to renal cell death. We previously demonstrated that several volatile anesthetics protect against renal IR injury and necrosis in rats in vivo. We subsequently showed that volatile anesthetics produced direct anti-inflammatory and anti-necrotic effects in cultured proximal tubule cells in vitro. In this study, we wanted to determine whether the volatile anesthetic isoflurane protects against renal IR injury by producing anti-inflammatory effects in mice. C57BL/6 mice subjected to renal IR under isoflurane anesthesia demonstrated improved renal function and reduced necrosis compared with mice subjected to renal IR under pentobarbital anesthesia. Mice subjected to renal IR under isoflurane anesthesia also showed a reduction in inflammation evidenced by a reduced renal influx of neutrophils and macrophages, reduced ICAM-1 expression, less upregulation of proinflammatory mRNAs (TNF-alpha, ICAM-1, KC, and IL-1beta) as well as reduced nuclear translocation of NF-kappaB 24 h after renal IR injury. Analysis of specific lymphocyte subset trafficking to the kidney using flow cytometry demonstrated that isoflurane anesthesia reduced intrarenal influx of CD3+, CD4+, CD8+, and NK1.1+ lymphocytes at 3 h after renal ischemia compared with pentobarbital anesthesia. However, only the differential reduction of NK1.1+ lymphocytes persisted 24 h after renal ischemia. Therefore, we conclude that isoflurane anesthesia significantly attenuated renal IR injury in mice by reducing inflammation and modulating leukocyte influx. In particular, neutrophil, macrophage, and NK1.1+ lymphocyte cell modulation may play a significant role in renal protection by isoflurane anesthesia.
authors.affiliation: Department of Anesthesiology,College of Physicians and Surgeons of Columbia University, New York, NY 10032-3784, USA. tl128@columbia.edu
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Lee
authors.forename: Mihwa
authors.initials: M
authors.lastname: Kim
authors.forename: Minjae
authors.initials: M
authors.lastname: Kim
authors.forename: NaLa
authors.initials: N
authors.lastname: Kim
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
mesh_terms: D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor; D007249:Inflammation / Q000517:prevention & control; D007377:Interleukin-3; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000517:prevention & control*; D007962:Leukocytes / Q000187:drug effects*; D051379:Mice; D009336:Necrosis / Q000517:prevention & control; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor; D007530:Isoflurane