Effects of tramadol and o-desmethyltramadol on canine innate immune system function

Axiak‐Bechtel, Sandra M.; Tsuruta, Kaoru; Amorim, Juliana; Donaldson, Rebecca; Lino, Giulia; Honaker, Allyson; Monibi, Farrah; Dodam, John R.; DeClue, Amy E.

doi:10.1111/vaa.12201

Cited by 13 publications

(10 citation statements)

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“…The other common analgesic administered to dogs with OSA in this study was tramadol. The immunologic effects of tramadol have been investigated in dogs, and tramadol did not alter cytokine production; therefore, it is hypothesized that tramadol was unlikely to affect the results of this study (Axiak-Bechtel et al, 2015).…”

Section: Discussionmentioning

confidence: 95%

Dogs with osteosarcoma have altered pro‐ and anti‐inflammatory cytokine profiles

Axiak‐Bechtel

Mathew

Amorim

et al. 2019

Veterinary Medicine & Sci

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BackgroundCurrent advances in immunotherapy are an exciting area of study in canine osteosarcoma (OSA). The objective of this study was to determine the immune response in dogs with osteosarcoma by measuring stimulated leukocyte production of tumor necrosis factor (TNF), interleukin (IL)‐6, IL‐10 and TNF and IL‐6 to IL‐10 ratios.MethodsWhole blood was collected from dogs with osteosarcoma receiving non‐steroidal anti‐inflammatory drugs (NSAIDs, n = 11), dogs with osteosarcoma not receiving NSAIDs (n = 14) and healthy dogs (n = 5).ResultsNo difference in TNF production was found among healthy and OSA dogs regardless of NSAID administration following stimulation with lipopolysaccharide (LPS) (p = .410), lipoteichoic acid (LTA) (p = .693) or PBS (p = .120). Leukocyte IL‐6 production was greater in all dogs with OSA after stimulation with LPS (p = .015), LTA (p = .014) and PBS (p = .034) with no difference between OSA dogs receiving NSAIDs and those not. No differences in IL‐10 were found among healthy controls and dogs with OSA regardless of NSAID use. There was no difference among groups for LPS‐stimulated TNF to IL‐10 ratios (p = .407). For LTA‐stimulated leukocytes, the TNF to IL‐10 ratio was lower in dogs with OSA than in healthy dogs (p = .031) with no difference between OSA NSAID dogs compared to OSA non‐NSAID dogs (p = .059). No differences were found in LPS (p = .310)‐ or LTA (p = .265)‐stimulated leukocyte IL‐6 to IL‐10 production ratios among groups.ConclusionsDogs with osteosarcoma have an altered pro‐ and anti‐inflammatory immunologic profile compared to healthy dogs regardless of NSAID use. Further study is indicated to determine the potential prognostic and therapeutic implications of these findings.

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Section: Discussionmentioning

confidence: 95%

Dogs with osteosarcoma have altered pro‐ and anti‐inflammatory cytokine profiles

Axiak‐Bechtel

Mathew

Amorim

et al. 2019

Veterinary Medicine & Sci

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Section: Methodsmentioning

confidence: 99%

“…Respiratory burst function in neutrophils and monocytes was determined with a Phagoburst kit according to the manufacturer's instructions (ORPEGEN Pharma) as previously described. 17 Briefly, 100 lL of heparinized blood from healthy and CI dogs was incubated with 20 lL of either opsonized E. coli (biological stimulus) or phorbol 12-myristate 13-acetate (PMA; chemical stimulus) for 10 min at 37°C in a water bath. Samples were then incubated with 20 lL of dihydrorhodamine-123 as a fluorogenic substrate for oxygen intermediates for 10 min at 37°C in a water bath.…”

Section: Methodsmentioning

confidence: 99%

“…A CyAn ADP flow cytometry instrument (Beckman Coulter, Inc.; Brea, CA, USA) and associated data analysis software (Summit V5.2.0.7477, Dako Colorado, Inc.; Ft. Collins, CO, USA) were used for analysis of phagocytosis and respiratory burst capacity in phagocytic cells, including neutrophils and monocytes, quantification of CD3 + /CD4 + , CD3 + /CD8 + , and CD21 + lymphoid phenotypes, and quantification of monocytic cells expressing HLA-DR and TLR-4 for all the dogs enrolled in this study using previously described methods. 14,[17][18][19] For phagocytosis and respiratory burst function, aggregation artifacts caused by bacteria or cells were excluded by gating around live cells based on DNA stain uptake (Fig 1). Gating of phagocytic cells, including both neutrophils and monocytes, was performed using forward versus side scatter.…”

Section: Methodsmentioning

confidence: 99%

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Immune Function in Critically Ill Dogs

Hoffman

Amorim

DeClue

2017

Veterinary Internal Medicne

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BackgroundPeople with critical illness (CI) commonly develop various forms of immune dysfunction, however, there is limited information concerning immune dysfunction in dogs with CI.HypothesisThe immune response in CI dogs differs from that of healthy dogs.AnimalsImmunologic variables were compared between 14 dogs with CI, defined as APPLEfast score of >20 points, admitted to the University of Missouri Veterinary Health Center Small Animal Clinic Intensive Care Unit and healthy controls (n = 15).MethodsCohort study evaluating constitutive and lipopolysaccharide (LPS)‐stimulated TNF‐α, IL‐6, and IL‐10 production, phagocytosis of opsonized E. coli and respiratory burst capacity after opsonized E. coli or phorbol 12‐myristate 13‐acetate (PMA) stimulation, peripheral blood lymphocyte phenotype, and monocyte expressions of HLA‐DR and TLR‐4.ResultsLipopolysaccharide‐stimulated leukocyte TNF‐α (median, Q1, Q3; CI, 49, 49, 120; control, 655, 446, 1174 pg/mL; P = < 0.001), IL‐6 (median, Q1, Q3; CI, 49, 49, 64; control, 100, 49, 166 pg/mL; P = 0.029), and IL‐10 (CI, 49, 49, 56; control, 96, 49, 203 pg/mL; P = 0.014) production and both E. coli (median, Q1, Q3; CI, 60.5, 43, 88.5; control, 86.6, 81, 89.2%; P = 0.047) and PMA (CI, 40, 11.7, 70; control, 93, 83, 97.6%; P = < 0.001)‐stimulated respiratory burst capacity significantly decreased in CI dogs. Percentage of monocytes expressing TLR‐4 greater in the CI dogs (median, Q1, Q3; CI, 46.9, 24.3, 64.2; control, 16.4, 9.4, 26.2%; P = 0.005).ConclusionThese findings suggest dogs with CI develop immune system alterations that result in reduced respiratory burst function and cytokine production despite upregulation of TLR‐4.

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“…Although not commonly used, tramadol appears to have antinociceptive effects in rodents and dog. 122,152,182,198,230 Tramadol is considered a drug with minimal immunosuppressive activity 11,122,182,198,230 although it can have profound antiinflammatory action and in some models be an immunostimulant. 23,181,230…”

Section: Surgerymentioning

confidence: 99%

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

DeMarco

Nunamaker

2019

comp med

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One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to balance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particular immune function or model are incomplete or don't exist. Further complicating the picture is evidence of the very tight integration and bidirectional functionality between the immune system and branches of the nervous system involved in nociception and pain. These relationships have advanced the concept of understanding pain as a protective neuroimmune function and recognizing pathologic pain as a neuroimmune disease. This review strives to summarize extant literature on the effects of pain and analgesia on immune system function and inflammation in the context of preclinical in vivo studies. The authors hope this work will help to guide selection of analgesics for preclinical studies of inflammatory disease and immune system function.

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Effects of tramadol and o-desmethyltramadol on canine innate immune system function

Cited by 13 publications

References 27 publications

Dogs with osteosarcoma have altered pro‐ and anti‐inflammatory cytokine profiles

Dogs with osteosarcoma have altered pro‐ and anti‐inflammatory cytokine profiles

Immune Function in Critically Ill Dogs

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

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