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Abstract

Introduction: Opioids alter immune responses and apoptotic pathways during sepsis in multiple species, and opioids are commonly used to recapitulate standard care protocols in canine models of inflammation. Despite the common use of opioids in canine models of inflammation, the immunomodulatory and apoptotic effects these drugs are largely unknown in this species. Hypothesis: The objective of this study was to evaluate effect of morphine, fentanyl or buprenorphine on canine whole blood phagocytic function, oxidative burst production capacity, leukocyte TNF production capacity, and lymphocyte apoptosis. Methods: Blood from six healthy, adult dogs was incubated with morphine (200 ng/mL), fentanyl (10 ng/mL), buprenorphine (10 ng/mL) or control (saline) for 3 (phagocytic function; oxidative burst; TNF production) or 8 (apoptosis) hours. Neutrophil phagocytosis of opsonized E. coli, respiratory burst capacity after opsonized E. coli or phorbol 12-myristate 13-acetate (PMA) stimulation, and annexin binding to apoptotic lymphocytes were evaluated using flow cytometry. Lipopolysaccharide and lipoteichoic acid-induced leukocyte TNF production was assessed using a bioassay. Data were compared using RMANOVA or Friedman’s test and Student-Newman-Keuls post hoc analysis (p <0.05 considered significant). Results: After PMA stimulation, neutrophils incubated with morphine had greater oxidative burst activity compared to control and buprenorphine treatments. Buprenorphine reduced lymphocyte apoptosis compared to morphine and control. Fentanyl did not have a significant treatment effect nor was there a difference in neutrophil phagocytosis or leukocyte cytokine production among the test solutions. Conclusions: These data indicate that opioids alter neutrophil oxidative burst capacity and lymphocyte apoptosis in dogs. While further work is needed to evaluate the immunomodulatory properties of opioids during various states of immune system activation, investigators should consider the possible impact of opioid immunomodulation when developing research protocols and interpreting immunologic data. This project was supported by the American Kennel Club Canine Health Foundation.