Interleukin-1, anorexia, and dietary fatty acids.
IL-1 and other cytokines mediate several components of both acute and chronic pathological processes observed in patients with cancer and chronic infection. Cachexia ranks as one of the more prominent aspects of several diseases and the present studies demonstrate that recombinant forms of either IL-1 beta or IL-1 alpha reduce food intake in experimental animals. In meal-fed rats, a single injection of IL-1 induces a 40% reduction [table: see text] in food intake, whereas daily injections slow normal weight gain. The anorexic response to IL-1 is prevented by cyclooxygenase inhibitors, although this is unlikely due to a central nervous system effect. Reduced production of cyclooxygenase products such as PGE2 also occurs in rats fed supplemental N-3 fatty acids, and this was associated with a decreased anorexic response to IL-1. Therefore, one mechanism by which IL-1 induces anorexia appears to require cyclooxygenase metabolites, such as PGE2. N-3 fatty acid supplements also reduce the severity of host responses to inflammation and infection. Part of this is due to decreased cyclooxygenase products; however, part also may be due to reduced synthesis of IL-1. Blood leukocytes from human subjects taking oral N-3 supplements produce 60% less IL-1. The ability of N-3 fatty acids to reduce IL-1 synthesis appears to be via the lipoxygenase pathway. Therefore, N-3 fatty acids may be beneficial to patients with anorexia, since such supplements would decrease both the anorexic response to IL-1 via reduced cyclooxygenase metabolites and the production of IL-1, via altered lipoxygenase metabolites.
Dinarello
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CA
Department of Medicine, Tufts University, Boston, Massachusetts.
Endres
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S
Meydani
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SN
Meydani
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M
Hellerstein
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MK
D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000517:prevention & control; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D001068:Feeding and Eating Disorders / Q000139:chemically induced*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004041:Dietary Fats; D005227:Fatty Acids; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha