Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs

Jaffey, Jared A.; Amorim, Juliana; DeClue, Amy E.

doi:10.1016/j.tvjl.2018.04.010

Cited by 19 publications

(21 citation statements)

References 34 publications

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“…Incubation of blood with calcitriol resulted in a decrease in leukocyte production of TNF-α, irrespective of the type of PAMP-exposure. This finding supports our hypothesis and corroborates results from previous studies that demonstrated calcitriol decreased leukocyte production of TNF-α in blood obtained from healthy and critically-ill dogs [11,21]. The molecular etiology for calcitriol induced modulation of TNF-α production in dogs is largely unknown.…”

Section: Discussionsupporting

confidence: 93%

“…Decreased 25-hydroxyvitamin (OH) D concentrations, the primary circulating metabolite of vitamin D, has been identified in many infectious diseases in dogs including leishmaniasis, babesiosis, spirocercosis, blastomycosis, and bacterial sepsis, which suggests that like people, vitamin D could have an important protective role in the canine innate immune response [16][17][18][19][20]. This theory is corroborated by early in vitro studies in healthy and critically ill dogs that demonstrated incubation of blood with calcitriol, decreased leukocyte production of the pro-inflammatory cytokine tumor-necrosis factor (TNF)-α in a concentration dependent manner [11,21]. These in vitro results that have highlighted the protective immunomodulatory functions of vitamin D have translated to yield in vivo benefits with oral supplementation of vitamin D in people.…”

Section: Introductionmentioning

confidence: 91%

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Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

Jaffey

Bessette

Tao

et al. 2020

Canine Genet Epidemiol

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Background: The active metabolite of vitamin D, calcitriol, has been shown across many different species to augment innate immune responses and dampen aberrant proinflammatory cytokine production. Community acquired infections are common in shelters and consume limited shelter resources, impact adoption rates, and can result in unnecessary euthanasia. Prophylactic oral vitamin D supplementation decreases the incidence and severity of upper and lower respiratory tract infections in humans. Before a clinical trial investigating the clinical benefit of oral vitamin D supplementation in shelter dogs can be pursued, an in vitro study evaluating the immunomodulatory effects of calcitriol in blood from shelter dogs is warranted. Therefore, the objective of this study was to determine if incubation of whole blood obtained from apparently healthy dogs housed in a shelter for ≥7 days with calcitriol would alter granulocyte/monocyte (GM) oxidative burst and phagocytic function as well as pathogen-associated molecular pattern (PAMP)-stimulated leukocyte production of tumor necrosis factor (TNF)-α, and interleukin (IL)-6, and IL-10. Results: Ten dogs housed in a shelter for ≥7 days were enrolled in a prospective cohort study. Whole blood from these dogs was incubated with calcitriol (10 − 7 M) or diluent (control) for 24 h. Subsequent to this incubation, phagocytosis of opsonized-Escherichia coli (E. coli) and E. coli-induced oxidative burst were evaluated via flow cytometry. In addition, leukocyte production of TNF-α, IL-6, and IL-10 were measured using a canine-specific multiplex bead assay. Calcitriol significantly decreased leukocyte TNF-α production (p = 0.009) and increased IL-10 production (p = 0.002). Tumor necrosis factor-α-toIL -10 ratio was significantly decreased with calcitriol (p = 0.017), while IL-6 production as well as GM oxidative burst and phagocytic function were not significantly affected. Conclusions: These data indicate that calcitriol attenuates proinflammatory immune responses without affecting GM oxidative burst or phagocytic function in vitro in whole blood obtained from apparently healthy shelter dogs.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 91%

Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

Jaffey

Bessette

Tao

et al. 2020

Canine Genet Epidemiol

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“…In people, vitamin A dampens inflammation by shifting CD4+ T-lymphocyte subtypes from T H 1 and T H 17 (pro-inflammatory) to T H 2 and T Reg (anti-inflammatory) (18). Moreover, vitamin D in people and dogs decreases leukocyte production of tumor-necrosis factor (pro-inflammatory) while concomitantly increasing interleukin-10 (anti-inflammatory) cytokines (18)(19)(20)(21). Future studies investigating the potential for repletion of vitamin D deficiency in dogs with SND are warranted.…”

Section: Discussionmentioning

confidence: 99%

Successful Long-Term Management of Canine Superficial Necrolytic Dermatitis With Amino Acid Infusions and Nutritionally Balanced Home-Made Diet Modification

et al. 2020

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A 10-year old, castrated male, Bichon Frise with a history of hyperadrenocorticism and intrahepatic portal vein hypoplasia was diagnosed with superficial necrolytic dermatitis (SND). The dog exhibited thick crusts on the chin, muzzle, prepuce, and paws. In addition, the dorsal surfaces of all paws were erythematous while the palmar/plantar surfaces were hyperkeratotic, hardened, and painful. The dog was treated with intravenous amino acid infusions (AAI), raw egg yolks, as well as zinc and omega-3 fatty acid oral supplements. The dog required AAI once every 2-3 weeks because this coincided with recrudescence of painful skin lesions. The dog was subsequently diagnosed with diabetes mellitus. A consult with the Nutrition Service was pursued 220 days after the original SND diagnosis because of concern for feeding raw eggs and for malnutrition since appetite was variable, muscle condition was reduced, and greater than 50% of ingested calories were from foods that were not nutritionally complete. There was also concern regarding the variability of the diet and the impact it would have on the management of diabetes mellitus. The diet was prepared by the dog owner according to a provided recipe and presented twice daily. The diet was rich in high quality protein and fat. All other treatments including medications, supplements, and bathing schedule remained unchanged at the time of diet modification. The dog was subclinical for SND associated clinical signs approximately 3 weeks after the diet modification, which also coincided with the last AAI. The AAI was postponed and was next administered 7 weeks later (i.e., 10 weeks from the previous infusion). The dog remained subclinical for SND related clinical signs and continued to receive AAI once every 10-12 weeks until he was euthanized 718 days later for complications related to severe multi-drug resistant, skin infections. In conclusion, this report highlights a novel role for nutritionally balanced home-made diets designed by a board-certified veterinary nutritionist could substantially increase time interval between AAI and outcome in dogs with SND.

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“…Hypovitaminosis D has been identi ed in many infectious diseases in dogs including leishmaniasis, babesiosis, spirocercosis, blastomycosis, and bacterial sepsis, which suggests that like people, vitamin D could have an important protective role in the canine innate immune response (16)(17)(18)(19)(20). This theory is corroborated by early in vitro studies in healthy and critically ill dogs that demonstrated incubation of blood with calcitriol, decreased leukocyte production of the pro-in ammatory cytokine tumor-necrosis factor (TNF)-α in a concentration dependent manner (11,21). These bench-top results that have highlighted the protective immunomodulatory functions of vitamin D have translated to yield in vivo bene ts with oral supplementation of vitamin D in people.…”

Section: Introductionmentioning

confidence: 91%

Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

Jaffey

Bessette

Tao

et al. 2020

Preprint

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Background The active metabolite of vitamin D, calcitriol, has been shown across many different species to augment innate immune responses and dampen aberrant proinflammatory cytokine production. Community acquired infections are common in shelters and consume limited shelter resources, impact adoption rates, and can result in unnecessary euthanasia. Prophylactic oral vitamin D supplementation decreases the incidence and severity of upper and lower respiratory tract infections in humans. Before a clinical trial investigating the clinical benefit of oral vitamin D supplementation in shelter dogs can be pursued, an in vitro study evaluating the immunomodulatory effects of calcitriol in blood from shelter dogs is warranted. Therefore, the objective of this study was to determine if incubation of whole blood obtained from apparently healthy dogs housed in a shelter for ≥ 7 days with calcitriol would alter granulocyte/monocyte (GM) oxidative burst and phagocytic function as well as pathogen-associated molecular pattern (PAMP)-stimulated leukocyte production of tumor necrosis factor (TNF)-α, and interleukin (IL)-6, and IL-10. Results Ten dogs housed in a shelter for ≥ 7 days were enrolled in a prospective cohort study. Whole blood from these dogs was incubated with calcitriol (10-7 M) or ethanol (control) for 24 h. Subsequent to this incubation phagocytosis of opsonized-Escherichia coli (E. coli) and E. coli-induced oxidative burst were evaluated via flow cytometry. In addition, leukocyte production of TNF-α, IL-6, and IL-10 were measured using a canine-specific multiplex assay. Calcitriol significantly decreased leukocyte TNF-α production (p = 0.009) and increased IL-10 production (p = 0.002). Tumor necrosis factor-α-to-IL-10 ratio was significantly decreased with calcitriol (p = 0.017), while IL-6 production as well as GM oxidative burst and phagocytic function were not significantly affected. Conclusions These data indicate that calcitriol attenuates proinflammatory immune responses without affecting GM oxidative burst or phagocytic function in vitro in whole blood obtained from apparently healthy shelter dogs.

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Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs

Cited by 19 publications

References 34 publications

Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

Successful Long-Term Management of Canine Superficial Necrolytic Dermatitis With Amino Acid Infusions and Nutritionally Balanced Home-Made Diet Modification

Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs

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