title: Effects of tramadol and o-desmethyltramadol on canine innate immune system function.
abstract: OBJECTIVE
  Tramadol is a commonly used opioid analgesic in dogs, particularly in dogs with a compromised immune system. An opioid may be selected for its immunomodulatory effects. Consequently, the objective of this study was to investigate the effects of tramadol on immune system function by evaluating the effect of tramadol and o-desmethyltramadol (M1) on the function of canine leukocytes in vitro. The hypothesis was that tramadol and M1 would not alter polymorphonuclear leukocyte (PMN) phagocytosis, PMN oxidative burst, or stimulated leukocyte cytokine production capacity of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10.
  
  
  METHODS
  In vitro pharmacodynamic study.
  
  
  METHODS
  Six healthy dogs.
  
  
  METHODS
  Blood from six dogs was obtained and incubated with various concentrations of tramadol and M1. Phagocytosis and oxidative burst were assessed using flow cytometry, and lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay.
  
  
  RESULTS
  No differences were detected in phagocytosis or oxidative burst with any drug concentration. Tramadol did not alter leukocyte cytokine production, however, M1 significantly blunted IL-10 production.
  
  
  CONCLUSIONS
  Tramadol and its metabolite M1 were sparing to PMN phagocytosis and oxidative burst in dogs in vitro. Tramadol did not alter leukocyte cytokine production, however, M1 blunted IL-10 production at clinically achievable concentrations suggesting that M1 may promote a proinflammatory shift.
  
  
  CONCLUSIONS
  These data suggest that tramadol has minimal effect on phagocytosis and oxidative burst, and may promote a proinflammatory shift. Therefore, tramadol may be an ideal opioid analgesic in dogs at high risk of infection. Further investigation in vivo is warranted.
authors.affiliation: Comparative Oncology Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Axiak-Bechtel
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuruta
authors.forename: Juliana
authors.initials: J
authors.lastname: Amorim
authors.forename: Rebecca
authors.initials: R
authors.lastname: Donaldson
authors.forename: Giulia
authors.initials: G
authors.lastname: Lino
authors.forename: Allyson
authors.initials: A
authors.lastname: Honaker
authors.forename: Farrah
authors.initials: F
authors.lastname: Monibi
authors.forename: John
authors.initials: J
authors.lastname: Dodam
authors.forename: Amy
authors.initials: A
authors.lastname: DeClue
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D014147:Tramadol / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; C080580:O-demethyltramadol; D014147:Tramadol
keywords: dog; immunomodulation; tramadol