title: Effects of opioids on phagocytic function, oxidative burst capacity, cytokine production and apoptosis in canine leukocytes.
abstract: Opioids alter immune and apoptotic pathways in several species. They are commonly used in companion animals affected with infectious and/or inflammatory disease, but the immunomodulatory and apoptotic effects of these drugs in dogs are relatively unknown. The aim of the present study was to evaluate the effects of morphine, buprenorphine and fentanyl on canine phagocyte function, oxidative burst capacity, leukocyte cytokine production, and lymphocyte apoptosis. Blood from six healthy adult dogs was incubated in the presence or absence of morphine (200 ng/mL), buprenorphine (10 ng/mL) or fentanyl (10 ng/mL) for 3 h (phagocytic function; cytokine production) or 8 h (apoptosis). Neutrophil phagocytosis of opsonized Escherichia coli, respiratory burst capacity after stimulation with opsonized E. coli or phorbol 12-myristate 13-acetate (PMA), and Annexin V-FITC staining of apoptotic lymphocytes were evaluated using flow cytometry. Leukocyte production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 was assessed after incubation with lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan. Morphine promoted a more intense respiratory burst. Morphine, buprenorphine and fentanyl all promoted LPS- or LTA-induced TNF-α and IL-10 production. However, the opioids tested did not alter TNF-α:IL-10 ratios. Morphine, buprenorphine and fentanyl all inhibited neutrophil apoptosis, an effect that was not concentration dependent in nature. These data indicate that opioids alter immune and apoptotic pathways in dogs. The possible effects of opioids on immune and cellular responses should be considered when designing studies and interpreting outcomes of studies involving administration of opioids in dogs.
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA. Electronic address: decluea@missouri.edu.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Declue
authors.affiliation: College of Veterinary Medicine, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, Korea.
authors.forename: Do-Hyeon
authors.initials: DH
authors.lastname: Yu
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Prochnow
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Axiak-Bechtel
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Amorim
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuruta
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Donaldson
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Lino
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: Farrah
authors.initials: F
authors.lastname: Monibi
authors.affiliation: Sarasota Dolphin Research Program, Chicago Zoological Society c/o Mote Marine Laboratory, Sarasota, FL, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Honaker
authors.affiliation: Comparative Internal Medicine Laboratory, College of Veterinary Medicine, University of Missouri, 900 East Campus Drive, Columbia, Missouri 65211, USA.
authors.forename: John
authors.initials: J
authors.lastname: Dodam
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002047:Buprenorphine / Q000009:adverse effects / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects; D004285:Dogs / Q000276:immunology / Q000502:physiology*; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects; D056747:Immunomodulation / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D002047:Buprenorphine; D009020:Morphine; D005283:Fentanyl
keywords: Immune response; Opioid; Pharmacodynamics