Effect of n-6 and n-3 fatty acids on expression of pro-inflammatory cytokines in lambs vaccinated against foot and mouth disease virus

Document Type : Original Research Articles (Regular Papers)


1 Department of Animal Science, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Agriculture Nuclear Research School, Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran, Karaj, Iran.

3 Department of Animal Science, Pishva-Varamin Branch, Islamic Azad University, Varamin, Iran.


The current study was aim to the effects of n-6 and n-3 polyunsaturated fatty acids (PUFA, or palmitic acid sources) on expression of pro-inflammatory cytokines in lambs vaccinated against foot and mouth disease (FMD) virus. A total of fifteen Sangsari male lambs with an age of 6 ± 1 months and body weight of 42 ± 1 kg were randomly assigned to one of three experimental treatments as follows: 1) PO: received calcium soap of palm oil fatty acid (FA) in the diet as source of palmitic acid (16:0), 2) SO: received calcium soap of sunflower oil FAs in the diet as source of linoleic acid (n-6 18:2) and 3) LO: received calcium soap of linseed oil FA in the diet as source of α-linolenic acid (n-3 18:3). The lambs were offered an iso-energetic and iso-nitrogenous diet for 28 days (including 21 days of adaptation and 7 days of sampling). The lambs were individually housed and had access to water ad libitum. The expression of interleukin-1β (IL-1β) mRNA was lower in LO when compared with PO and SO (P<0.05). The expression of tumor necrosis factor-α (TNFα) mRNA was higher in PO when compared with SO and LO and the lowest expression of TNFα mRNA was measured in LO (P<0.05). Lower concentrations of serum cholesterol and triglyceride (TG) were measured in vaccinated lambs on LO diet when compared with vaccinated lambs on palmitic FA diet (P<0.05). There was no significant difference between SO and LO groups in serum cholesterol or TG levels. There were no significant differences between treatments (P>0.05) in serum level of total proteins and albumin. The findings from the current study showed feeding α-linolenic acid diet following vaccination against FMD resulted in a decrease in serum levels of cholesterol and TG due to higher n-3 PUFA intake and suppressed the pro-inflammatory cytokine expression (IL-1 and TNFα).  


Main Subjects

Al-Khalaifah, H., 2020. Modulatory effect of dietary polyunsaturated fatty acids on immunity, represented by phagocytic activity. Frontiers in Veterinary Science 7, 672-681.
Alagawany, M., Elnesr, S.S., Farag, M.R., El-Sabrout, K., Alqaisi, O., Dawood, M.A., Soomro, H., Abdelnour, S.A., 2020. Nutritional significance and health benefits of omega-3,-6 and-9 fatty acids in animals. Animal Biotechnology 1-13.
Anil, G., Gurudutt, J., 2011. Metabolic profile of foot and mouth disease stressed sheep in semi arid region. Journal of Stress Physiology and Biochemistry 7, 25-34.
Barkakati, J., Sarma, S., Kalita, D., 2015. Effect of foot and mouth disease on haematological and biochemical profile of cattle. Indian Journal of Animal Research 49, 713-716.
Belsham, G.J., 1993. Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure. Progress in Biophysics and Molecular Biology 60, 241-260.
Benoit, M., Desnues, B., Mege, J.L., 2008. Macrophage polarization in bacterial infections. The Journal of Immunology 181, 3733-3739.
Bertoni, G., Minuti, A., Trevisi, E., 2015. Immune system, inflammation and nutrition in dairy cattle. Animal Production Science 55, 943-948.
Bertoni, G., Trevisi, E., Han, X., Bionaz, M., 2008. Effects of inflammatory conditions on liver activity in puerperium period and consequences for performance in dairy cows. Journal of Dairy Science 91, 3300-3310.
Bhathena, S.J., 2006. Relationship between fatty acids and the endocrine and neuroendocrine system. Nutritional Neuroscience 9, 1-10.
Calder, P.C., Yaqoob, P., Thies, F., Wallace, F.A., Miles, E.A., 2002. Fatty acids and lymphocyte functions. British Journal of Nutrition 87, 31-48.
Chinsangaram, J., Piccone, M.E., Grubman, M.J., 1999. Ability of foot-and-mouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. Journal of Virology 73, 9891-9898.
Coggins, M., Rosenzweig, A., 2012. The fire within: Cardiac inflammatory signaling in health and disease. Circulation Research 110, 116-125.
Colonna, M., Krug, A., Cella, M., 2002. Interferon-producing cells: On the front line in immune responses against pathogens. Current Opinion in Immunology 14, 373-379.
Darwesh, A.M., Sosnowski, D.K., Lee, T.Y., Keshavarz-Bahaghighat, H., Seubert, J.M., 2019. Insights into the cardioprotective properties of n-3 pufas against ischemic heart disease via modulation of the innate immune system. Chemico-Biological Interactions 308, 20-44.
De Los Santos, T., Diaz-San Segundo, F., Grubman, M.J., 2007. Degradation of nuclear factor kappa b during foot-and-mouth disease virus infection. Journal of Virology 81, 12803-12815.
Dervishi E, Serrano C, Joy M, Serrano M, Rodellar C, Calvo J.H. 2010. Effect of the feeding system on the fatty acid composition, expression of the Δ9-desaturase, Peroxisome Proliferator-Activated Receptor Alpha, Gamma, and Sterol Regulatory Element Binding Protein 1 genes in the semitendinous muscle of light lambs of the Rasa Aragonesa breed. BMC Veterinary Research 6, 1-11.
Ebrahimi, M., Rajion, M.A., Goh, Y.M., 2014. Effects of oils rich in linoleic and α-linolenic acids on fatty acid profile and gene expression in goat meat. Nutrients 6, 3913-3928.
Feingold, K., Soued, M., Staprans, I., Gavin, L., Donahue, M., Huang, B., Moser, A., Gulli, R., Grunfeld, C., 1989. The effect of tnf on lipid metabolism in the diabetic rat: Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for tnf induced hyperlipidemia. The Journal of Clinical Investigation 83, 1116-1121.
Ghanem, M.M., Abdel-Hamid, O.M., 2010. Clinical, haematological and biochemical alterations in heat intolerance (panting) syndrome in egyptian cattle following natural foot-and-mouth disease (fmd). Tropical Animal Health and Production 42, 1167-1173.
Griinari, J., Corl, B., Lacy, S., Chouinard, P., Nurmela, K., Bauman, D., 2000. Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by δ9-desaturase. The Journal of Nutrition 130, 2285-2291.
Gulliver, C.E., Friend, M.A., King, B.J., Clayton, E.H., 2012. The role of omega-3 polyunsaturated fatty acids in reproduction of sheep and cattle. Animal Reproduction Science 131, 9-22.
Hadfield, J.M., 2017. Characterization of the immune response to lipopolysaccharide in early pregnant ewes as a model to study bacterial infection induced embryonic loss. Graduate Theses, Dissertations, and Problem Reports. 5731.
Hirayama, D., Iida, T., Nakase, H., 2018. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. International Journal of Molecular Sciences 19, 92-104.
Ikeda, I., Cha, J.-Y., Yanagita, T., Nakatani, N., Oogami, K., Imaizumi, K., Yazawa, K., 1998. Effects of dietary α-linolenic, eicosapentaenoic and docosahexaenoic acids on hepatic lipogenesis and β-oxidation in rats. Bioscience, Biotechnology, and Biochemistry 62, 675-680.
Kaveh, M., Eftekhar, N., Boskabady, M.H., 2019. The effect of alpha linolenic acid on tracheal responsiveness, lung inflammation, and immune markers in sensitized rats. Iranian Journal of Basic Medical Sciences 22, 255-261.
Kovacsovics-Bankowski, M., Clark, K., Benacerraf, B., Rock, K.L., 1993. Efficient major histocompatibility complex class i presentation of exogenous antigen upon phagocytosis by macrophages. Proceedings of the National Academy of Sciences 90, 4942-4946.
Kumamoto, T., Ide, T., 1998. Comparative effects of α‐and γ‐linolenic acids on rat liver fatty acid oxidation. Lipids 33, 647-654.
Lakdawala, N., Grant-Kels, J.M., 2015. Acrodermatitis enteropathica and other nutritional diseases of the folds (intertriginous areas). Clinics in Dermatology 33, 414-419.
Lee, I.K., Kye, Y.C., Kim, G., Kim, H.W., Gu, M.J., Umboh, J., Maaruf, K., Kim, S.W., Yun, C.-H., 2016. Stress, nutrition, and intestinal immune responses in pigs—a review. Asian-Australasian Journal of Animal Sciences 29, 1075.
Loor, J.J., Bertoni, G., Hosseini, A., Roche, J.R., Trevisi, E., 2013. Functional welfare–using biochemical and molecular technologies to understand better the welfare state of peripartal dairy cattle. Animal Production Science 53, 931-953.
Ma, X.-x., Ma, L.-n., Chang, Q.-y., Ma, P., Li, L.-J., Wang, Y.-y., Ma, Z.-r., Cao, X., 2018. Type i interferon induced and antagonized by foot-and-mouth disease virus. Frontiers in Microbiology 9, 1-8.
Majewska, M.P., Pająk, J.J., Skomiał, J., Kowalik, B., 2016. The effect of different forms of sunflower products in diets for lambs and storage time on meat quality. Animal Feed Science and Technology 222, 227-235.
Matsuyama, W., Mitsuyama, H., Watanabe, M., Oonakahara, K.-i., Higashimoto, I., Osame, M., Arimura, K., 2005. Effects of omega-3 polyunsaturated fatty acids on inflammatory markers in copd. Chest 128, 3817-3827.
Mosser, D.M., Edwards, J.P., 2008. Exploring the full spectrum of macrophage activation. Nature Reviews Immunology 8, 958-969.
Nahed, S., 2010. Investigation of serum insulin and cortisol concentrations in foot and mouth disease-infected cattle in relation to changes in serum biochemical variables and protein electrophoretic fractionation profile. Global Veterinaria 4, 450-455.
Nath, R., Das, S., Sarma, S., Devi, M., 2014. Comparison of blood profiles between healthy and brucella affected cattle. Veterinary World 7, 668-670.
Nian, M., Lee, P., Khaper, N., Liu, P., 2004. Inflammatory cytokines and postmyocardial infarction remodeling. Circulation Research 94, 1543-1553.
Orsel, K., Dekker, A., Bouma, A., Stegeman, J.A., De Jong, M.C.M., 2007. Quantification of foot and mouth disease virus excretion and transmission within groups of lambs with and without vaccination. Vaccine 25, 2673-2679.
Park, J.H., Kim, S.J., Oem, J.K., Lee, K.N., Kim, Y.J., Kye, S.J., Park, J.Y., Joo, Y.S., 2006. Enhanced immune response with foot and mouth disease virus vp1 and interleukin-1 fusion genes. Journal of Veterinary Science 7, 257-262.
Powanda, M., 1980. Host metabolic alterations during inflammatory stress as related to nutritional status. American Journal of Veterinary Research 41, 1905-1911.
Rowe, A., Macedo, F., Visentainer, J., Souza, N., Matsushita, M., 1999. Muscle composition and fatty acid profile in lambs fattened in drylot or pasture. Meat Science 51, 283-288.
Schwager, J., Richard, N., Riegger, C., Salem, N., 2015. Ω-3 pufas and resveratrol differently modulate acute and chronic inflammatory processes. BioMed Research International 2015, 1-11.
Sebastian, R., Sravanthi, M., Umapathi, V., Krishnaswamy, N., Priyanka, M., Dechamma, H., Ganesh, K., Basagoudanavar, S.H., Sanyal, A., Reddy, G., 2020. Foot and mouth disease virus undergoes non-progressive replication in mice peritoneal macrophages and induces m1 polarization. Virus Research 281, 197906.
Seo, J., Song, M., Jo, N., Kim, W., Jeong, S., Kim, J., Lee, S., Seo, S., 2019. The co-injection of antioxidants with foot-and-mouth disease vaccination altered growth performance and blood parameters of finishing holstein steers. Asian-Australasian Journal of Animal Sciences 32, 792-799.
Shi, L., Xu, Y., Mao, C., Wang, Z., Guo, S., Jin, X., Yan, S., Shi, B., 2020. Effects of heat stress on antioxidant status and immune function and expression of related genes in lambs. International Journal of Biometeorology 64, 2093-2104.
Simopoulos, A.P., 2002. Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition 21, 495-505.
Smeed, J.A., Watkins, C.A., Rhind, S.M., Hopkins, J., 2007. Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis. BMC Veterinary Research 3, 1-11.
Winnik, S., Lohmann, C., Richter, E.K., Schäfer, N., Song, W.-L., Leiber, F., Mocharla, P., Hofmann, J., Klingenberg, R., Borén, J., 2011. Dietary α-linolenic acid diminishes experimental atherogenesis and restricts t cell-driven inflammation. European Heart Journal 32, 2573-2584.
Yaqoob, P., Pala, H., Cortina-Borja, M., Newsholme, E.A., Calder, P.C., 2000. Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. European Journal of Clinical Investigation 30, 260-274.
Zeng, Y.-Y., Jiang, W.-D., Liu, Y., Wu, P., Zhao, J., Jiang, J., Kuang, S.-Y., Tang, L., Tang, W.-N., Zhang, Y.-A., 2016. Dietary alpha-linolenic acid/linoleic acid ratios modulate intestinal immunity, tight junctions, anti-oxidant status and mrna levels of nf-κb p65, mlck and nrf2 in juvenile grass carp (ctenopharyngodon idella). Fish and Shellfish Immunology 51, 351-364.