In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress

Background: Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of omega 6 to omega 3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The omega 3 PUFAs reduce the production of proinflammatory cytokines. Methods: This study examines whether an imbalance in omega 6 to omega 3 PUFAs in human blood predicts a greater production of proinflammatory cytokines in response to psychologic stress. Twenty-seven university students had serum sampled a few weeks before and after as well as I day before a difficult oral examination. We determined the omega 6 and omega 3 fractions in serum phospholipids as well as the ex vivo production of IFN-gamma, TNF-alpha, IL-6, IL-10, and IL-5 by diluted whole blood stimulated with polyclonal activators. Results: Academic examination stress significantly increased the ex vivo, stimulated production of IFN-gamma, TNF-alpha and IL-10, and the IFN-gamma/IL-5 production ratio. Subjects with lower serum omega 3 PUFA levels or with a higher omega 6/omega 3 ratio had significantly greater stress-induced TNF-alpha and IFN-gamma responses than subjects with higher serum omega 3 PUFAs and a lower omega 6/omega 3 ratio, respectively. Subjects with lower serum omega 3 PUFA levels or with a higher omega 6/omega 3 ratio had a significantly higher stress-induced increase in the IFN-gamma/IL-5 ratio than the remaining subjects. Conclusions: Psychologic stress induces a Th-1-like or proinflammatory response in some subjects. An imbalance in the omega 6 to omega 3 PUFA ratio appears to predispose humans toward an exaggerated Th-I-like response and an increased production of monocytic cytokines, such as TNF-alpha, in response to psychologic stress. The results suggest that increased omega 3 PUFA levels may attenuate the proinflammatory response to psychologic stress. (C) 2000 Society of Biological Psychiatry.