Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward the Th2 pole by suppression of Th1 development.

We showed that dietary long-chain (n-3) PUFAs present in fish oil (FO) affect CD4(+) T cell proliferation and cytokine production in C57BL/6 mice. To test the hypothesis that the anti-inflammatory effect of dietary (n-3) PUFAs could be due to the indirect suppression of T helper (Th)1 cells by cross-regulation of enhanced Th2 activation, mice were fed a wash-out control diet [5% corn oil (CO), (n-6) PUFA] for 1 wk, followed by the control diet or a fish oil diet [1% CO + 4% FO, (n-3) PUFA] for 2 wk. Splenic CD4+ T cells were cultured under both neutral and Th2 polarizing conditions for 2 d. Cells were reactivated and analyzed for interleukin-4 and interferon-gamma by intracellular cytokine staining. Dietary fish oil significantly increased the percentage of Th2 polarized cells and suppressed Th1 cell frequency under neutral conditions. However, under Th2 polarizing conditions, although the suppression of Th1 cells was maintained in FO-fed mice, no effect was observed in Th2 cells. Dietary fish oil increased the Th2/Th1 ratio in the presence of homologous mouse serum under both neutral (P = 0.0009) and Th2 polarizing conditions (P = 0.0185). The FO diet did not significantly affect proliferation under Th2 polarizing conditions. Thus, the anti-inflammatory effects of FO may be explained in part by a shift in the Th1/Th2 balance, due to the direct suppression of Th1 development, and not by enhancement of the propensity of CD4+ T cells to be polarized toward a Th2 phenotype, at least in vitro.