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 γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of ω6 to ω3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The ω3 PUFAs reduce the production of proinflammatory cytokines. Methods: This study examines whether an imbalance in ω6 to ω3 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 ω6 and ω3 fractions in serum phospholipids as well as the ex vivo production of IFN-γ, TNF-α, 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-γ, TNF-α and IL-10, and the IFN-γ/IL-5 production ratio. Subjects with lower serum ω3 PUFA levels or with a higher ω6/ω3 ratio had significantly greater stress-induced TNF-α and IFN-γ responses than subjects with higher serum ω3 PUFAs and a lower ω6/ω3 ratio, respectively. Subjects with lower serum ω3 PUFA levels or with a higher ω6/ω3 ratio had a significantly higher stress-induced increase in the IFN-γ/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 ω6 to ω3 PUFA ratio appears to predispose humans toward an exaggerated Th-1–like response and an increased production of monocytic cytokines, such as TNF-α, in response to psychologic stress. The results suggest that increased ω3 PUFA levels may attenuate the proinflammatory response to psychologic stress.