title: Effects of buprenorphine and estrous cycle in a murine model of cecal ligation and puncture.
abstract: The effect of opioids on the immunopathology of sepsis models in mice has been controversial. In previous work, we showed that mortality and various inflammatory parameters did not differ between female mice given saline or buprenorphine after cecal ligation and puncture. To investigate further, we hypothesized that buprenorphine would not affect outcomes of sepsis at any stage of estrous. Female mice were allocated into 4 groups (n = 20 per group) according to stage of estrous. Mice then underwent cecal ligation and puncture and received either buprenorphine or saline. In 3-wk survival studies, overall survival did not differ between buprenorphine- and saline-treated mice. When mice were stratified according to stage of estrous, survival did not vary among saline-treated groups but was lower in buprenorphine-treated mice in metestrus compared with proestrus. To investigate inflammation as a potential mechanism for survival, we measured cell counts and cytokine levels in the peripheral blood and peritoneal lavage fluid at 12 and 24 h after cecal ligation and puncture. At 24 h, buprenorphine-treated mice in proestrus had more circulating neutrophils and monocytes than did saline-treated mice in proestrus and more circulating WBC than did mice in any other stage with or without buprenorphine. Our current results suggest that the effects of buprenorphine on a 50% survival model of sepsis in BALB/c female mice are minimal overall but that the stage of estrous has various effects in this model. Investigators should consider the effects of buprenorphine and estrous cycle when using female mice in sepsis research.
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA. Lucy.kennedy@case.edu.
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Kennedy
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Haejin
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: A Marissa
authors.initials: AM
authors.lastname: Wolfe
authors.affiliation: Department of Small Animal Clinical Sciences, Veterinary Medical Center, Michigan State University College of Veterinary Medicine, East Lansing, Michigan, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hauptman
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Nemzek-Hamlin
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000382:microbiology; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D002432:Cecum / Q000382:microbiology / Q000601:surgery*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D030762:Estrous Cycle; D004971:Estrus; D005260:Female; D018836:Inflammation Mediators / Q000097:blood; D008026:Ligation; D008686:Metestrus; D051379:Mice; D008807:Mice, Inbred BALB C; D010537:Peritoneum / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D011359:Proestrus; D011677:Punctures; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D018836:Inflammation Mediators; D002047:Buprenorphine