Modulation of Cytokine Production by Dietary Polyunsaturated Fatty Acids

Abstract

The existence of a bidirectional interaction between nutrition, host defense, and infectious, inflammatory and neoplastic diseases is well established. The nutritional status of a host has a profound effect on the immune response and its ability to defend against invading pathogens. On the other hand, the metabolic changes associated with these diseases can adversely affect the nutritional status of the host. Cytokines play an important role in both aspects of this interrelationship. Both the production and biologic function of cytokines are regulated by eicosanoids (1). Thus, it is imperative to study the effect of dietary fatty acid, precursors of eicosanoids, on the production and biologic function of cytokines. The production of several cytokines, such as interleukin (IL)-1, IL-2 and tumor necrosis factor (TNF), has been shown to be decreased by prostaglandin (PG) E₂ (2–6). Lipoxygenase products have been shown either to decrease or increase cytokine production (7). Some of the biologic effects of cytokines, i.e., fever induction, appetite loss, and inflammation, are believed to be mediated by PGE₂ (2).

Cytokines

Cytokines are protein mediators that serve as communication signals among different cells. The cells of the immune system are the main source of cytokines, although other cell types such as fibroblasts, keratino-cytes, and endothelial cells are also capable of synthesizing these substances. Similarly, cytokines act on targets that can include both immune and nonimmune cell types, further expanding their physiologic and pathologic scope beyond the immune system. A notable feature of cytokines is that they act as both “mediators of defense” and “mediators of disease.” As mediators of defense, these compounds are essential in the T eell response, antibody formation, tumor killing, hematopoiesis, nonspecific resistance, radio protection, and anti-inflammation. As mediators of disease, they induce fever, inflammation, pain, metabolic dysfunction, tissue degradation, anorexia, cachexia, shock, and death (1). Cytokines have been implicated in the pathogenesis of several diseases, including cardiovascular, bone, joint, and skin diseases. More than a dozen cytokines have been characterized and several are available in recombinant form.