By the scientific direction of NBF – LANES with the advice of Dr. Paola Persico
Cytokines have an indispensable role in proper immune response, but the overproduction can be detrimental to the host organism and can cause: alterations in some organs (heart function), anorexia, cachexia and non-regenerative anemia.
Cytokines are multifunctional peptides produced by the body, above all, by lymphocytes and macrophages activated during immune reactions and in the inflammatory process (Collins, 1999).
The cytokines promote many “defense mechanisms” within the organism including hyperthermia, the production of acute phase proteins, hypotension, activation and neutrophilic chemotaxis, activation of B and T lymphocytes, the increase of the synthesis of mediators of lipid metabolism as well as prostaglandin, leukotriene and platelet activating factor (PAF) (Collins, 1999; Dinarello, 1996; Calder, 1997). The most important cytokines released by the macrophages are: tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) (Calder, 2001). The increased release of TNF-α, IL-1ß and IL-6 is considered a marker of septic shock and bleeding (Jarrar, 1999).
The effects induced by TNF-α, IL-1 and IL-6 are essential during the acute phase of the immune response against pathogens. They have an indispensable role in proper immune response, but the overproduction can be detrimental to the host organism. Overproduction and / or the continuous production can lead, just to name a few, alterations in bone remodeling and cartilage, alterations in some organs (heart function), anorexia, cachexia and non-regenerative anemia (Jarrar, 1999; Dinarello, Gelin, 1991 Strassmann, 1995). The ability to control these mediators allows limiting damage especially in the course of chronic inflammatory diseases. The integration use of fatty acids Omega-3 as a supplement in feed rations seems to have a good anti-inflammatory effect (heart disease, cardiac cachexia, cancer cachexia).
Cytokines are not the only mediators of the immune response and the body’s inflammatory process, among others are prostaglandins, leukotrienes, PAF. Prostaglandin E2 (PGE2) is a metabolite of arachidonic acid produced predominantly by macrophages, PGE2 plays a fundamental role in the local inflammatory response as well as in the exudation and in the erythema and systematically causes hyperthermia (Collins, 1999; Tilley, 2001 ). PAF is derived from the activation of mediators of phospholipid metabolism (Collins, 1999). As of today is known the role of PAF in the peripheral capillary circulation, in the gas exchange at the alveolar level, in increasing vascular permeability in the bronchial spasm, in adhesion and in the chemotaxis processes of neutrophils and eosinophils (Kroegel, 1994; Christie , 2002). PAF acts by stimulating the synthesis of TNF-α and IL-1 by activated macrophages (Kroegel, 1994; Christie, 2002).
HOW TO CONTROL CYTOKINE TNF-Α, IL-1, IL-6 AND PAF
The research aimed at understanding the metabolic pathways designed to block and / or inhibit the synthesis of these inflammatory mediators are subjects of ongoing interest. The ability to control TNF-α, IL-1, IL-6 and PAF would result in the possibility of minimizing the negative effects in chronic inflammatory diseases. Currently on the market numerous anti-inflammatory drugs are available but, in addition to problems of cost, can have significant side effects, especially if used for long periods. Dietary supplementation of Omega-3 fats has been suggested as one of the possible methods for modulating the immune response while avoiding the toxic side effects of its anti-inflammatory drugs.
The results of the studies show that supplementation with fatty acids with a ratio Omega 6 and Omega 3 of 3.4:1 can be associated with a significant reduction in blood concentration and the activity of IL-1, IL-6 and PGE2. These scientific evidences support the hypothesis that the use of EPA and DHA may be regarded as an integral part of an anti-inflammatory treatment for those affected dogs, for example, from chronic inflammatory diseases. In patients with osteoarthritis the inflammatory cells of synovial origin release several mediators that cause a degeneration of the cartilage matrix by chondrocytes. The Omega 3 fatty acids, in particular EPA, compete with arachidonic acid for the same enzymes and inhibit the release, thus causing a greater production of anti-inflammatory eicosanoids compared to pro-inflammatory. It was observed (HW Sinclair, 1984) that prostaglandins, resulting from the metabolic pathway of arachidonic acid and produced by osteogenic cells combine to regulate the formation and bone resorption. In diets supplemented with Omega 3 there is a lower production of PGE2 and this can be very important in the management of a patient suffering from bone degeneration processes (osteoarthritis, weakness, etc.). The ratio of fatty acids Omega 3: Omega 6 is important because eicosanoids derived by the acid eicosapentaenoic are less pro-inflammatory vs. those derived from arachidonic acid.
Recent studies suggest that the use of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), active ingredients of Omega-3 fatty acids contained in fish and / or fish oils, decrease the production of TNF-α, PGE2, IL -1 and IL-6 and are a valuable tool in the management of chronic inflammatory diseases both in Human Medicine and in Veterinary Medicine (LeBlanc, 2008).
Short bibliography:
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– Collins T “Acute and chronic inflammation” Robbins pathologic basis of disease, 6th ed. WB Saunders, 1999
– Calder PC “Polynsaturated fatty acids, inflammation and immunity” Lipids 36: 1007-24; 2001
– Calder PC “Polynsaturated fatty acids and cytokine production in health and disease” Am Nutr Metab 41: 203-34; 1997
– Dinarello CA “Biologic basis for interleukin-1 in disease” Blood 1996; 87: 2095-2147
– J Gelin, Moldawer L, et al Lonnroth C “Role of endogenous tumor necrosis factor a and interleukin 1 for experimental rumor growth and the development of Cancer cachexia ” Cancer Res 1991; 51: 415-421
– Sinclair HW “Essential fatty acids in perspective” Human Nutrition: Clin Nutrit 38C: 245-60; 1984
– Strassmann G “Inhibition of experimental cancer cachexia by anti-cytokine-receptor therapy “
Citokines Mol Ther 107-13; 1995
– Tiley SL “Mixed messages: modulation of inflammation and immune responses by prostaglandins and tromboxanes “J Clin Invest 108: 15-23; 2001
– Kroegel C “Pulmonaryimmune cells in health and disease: the eosinophil leucocyte “Eur Respir J 7: 519-43; 1994
– Christie PE “Lipid inflammatory mediators: leukotrienes, prostaglandins, platelet- activating factor “Allergy Clin Immunol 16: 233-54; 2002
– CJ LeBlanc, Horohov DW et al “Effects of dietary supplementation with fish oil on the in vivo production of inflammatory mediators in clinically normal dogs “AJVR 2008; vol 69, 4: 486-493
