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

Abstract:

BACKGROUND: Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon (IFN- ), tumor necrosis factor (TNF- ), 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 1 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- , TNF- , 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- , TNF- and IL-10, and the IFN- /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- and IFN- 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- /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-1-like response and an increased production of monocytic cytokines, such as TNF- , in response to psychologic stress. The results suggest that increased omega-3 PUFA levels may attenuate the proinflammatory response to psychologic stress.