Effect of age, breed and dietary omega-6 (n-6): Omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs

University of Dayton, Dayton, OH 45469, USA
Veterinary Immunology and Immunopathology (Impact Factor: 1.54). 09/1999; 69(2-4):165-183. DOI: 10.1016/S0165-2427(99)00052-5


The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6) : (n-3) ratio of 25 : 1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6) : (n-3) ratio of 5 : 1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-α production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence α-tocopherol status although older dogs had significantly lower serum α-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6) : (n-3) fatty acid ratio of 5 : 1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs

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    • "Nevertheless, canine macrophages in allergic reactions are low IFNγ producers and synthesize IL-4 (Fujiwara et al. 2003); this makes them similar to mouse M2 macrophages. Moreover, the blunted inflammatory activation of canine macrophages in response to adenosine and ATP (Fujimoto et al. 2012) and the increased prostaglandin production in response to ω-3 fatty acids (Kearns et al. 1999) resemble features of mouse M2 macrophages. "
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    ABSTRACT: The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.
    Cell and Tissue Research 08/2015; DOI:10.1007/s00441-015-2253-1 · 3.57 Impact Factor
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    • "However, not only the PUFA content, which was similar among diets, but also the amount of specific FA, play an important role in the initiation of lipid peroxidation; the greater the degree of unsaturation the more vulnerable to lipid peroxidation [41]. Muggli proposed a formula taking into account mixtures of FA [33]. Both diets used in the present study contained higher levels of α-tocopherol compared to this recommendation (calculated according to Muggli [48]: MFn-3 diet: 41.2 vitamin E mg/kg diet; HFn-6 diet: 42.0 vitamin E mg/kg diet). "
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    ABSTRACT: Background Oxidative stress and inflammation can be altered by dietary factors in various species. However, little data are available in true carnivorous species such as domestic cats. As numerous anti-inflammatory and anti-oxidative additives become available and might be of use in cats with chronic low-grade inflammatory diseases, the current study aimed to develop a model of diet-induced inflammation by use of two opposite diets. It was hypothesized that a high fat diet enhanced in n-6 PUFA and with lower concentrations of antioxidants would evoke inflammation and oxidative stress in domestic cats. Results Sixteen healthy adult cats were allocated to two groups. One group received a moderate fat diet, containing pork lard and salmon oil (AA:(EPA + DHA) ratio 0.19) (MFn-3), while the other group was fed a high fat diet, containing pork lard and chicken fat (AA:(EPA + DHA) ratio 2.06) (HFn-6) for 12 weeks. Prior to and 2, 4, 6, 8, 10 and 12 weeks after starting the testing period, blood samples were collected. Erythrocytic fatty acid profile showed clear alterations in accordance to the dietary fatty acid profile. Serum thiobarbituric acid reactive substances was higher when fed MFn-3 compared to the HFn-6, suggesting augmented oxidative stress. This was associated with a reduced serum vitamin E status, as serum α-tocopherol concentrations were lower with MFn-3, even with higher dietary levels of vitamin E. Serum cytokine and serum amyloid A concentrations were not influenced by diet. Conclusion These results point towards a resistance of cats to develop dietary fat-induced inflammation, but also suggest a high susceptibility to oxidative stress when fed a fish oil-supplemented diet even with moderate fat level and additional vitamin E.
    BMC Veterinary Research 05/2014; 10(1):104. DOI:10.1186/1746-6148-10-104 · 1.78 Impact Factor
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    • "Gonzalez et al. (2000) suggested that the immune surveillance of the host could be important for CTVT regression during vincristine chemotherapy; this theory implies that a diminished immunological reaction of the host should reduce tumor clearance during chemotherapy. In this context, the age-associated decline of cellular and humoral defense mechanisms in dogs (Kearns et al., 1999) might explain the delayed vincristine induced tumor regression in older animals. Although it seems plausible that a larger tumor would take more time to regress completely than a smaller one, it would also be expected that the former might produce greater amount of immune-suppressive factors, which could retard tumor clearance. "
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    ABSTRACT: Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression.
    The Veterinary Journal 03/2010; 183(3-183):362-363. DOI:10.1016/j.tvjl.2008.11.009 · 1.76 Impact Factor
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