1. The effects of a variety of fatty acids on human peripheral blood lymphocyte proliferation stimulated by concanavalin A or purified protein derivative of Mycobacterium tuberculosis were studied.
2. The proliferative response to concanavalin A was inhibited by all of the polyunsaturated fatty acids tested (eicosapentaenoate, arachidonate, docosahexaenoate, linoleate and α-linolenate) and also by the saturated fatty acid, stearate. The greatest inhibition of proliferation (approximately 85%) was caused by eicosapentaenoate.
3. The proliferative response to the purified protein derivative of Mycobacterium tuberculosis was inhibited by all of the polyunsaturated fatty acids tested, except α-linolenate, and also by stearate. The greatest inhibition of proliferation (approximately 75%) was caused by eicosapentaenoate.
4. The pattern of inhibition of proliferation by fatty acids was similar to that previously reported for rat lymphocytes with one exception: oleate did not inhibit human lymphocyte proliferation.
5. The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2. In the presence of mitogen the concentration of interleukin-2 in the culture medium increased markedly above that in the medium of non-stimulated cells.
6. All polyunsaturated fatty acids tested caused a decrease in the concentration of interleukin-2; the greatest decrease (approximately 90%) was caused by eicosapentaenoate.
7. There was a good correlation between lymphocyte proliferation in the presence of fatty acids and interleukin-2 concentration. However, stearate did not decrease the interleukin-2 concentration but did inhibit lymphocyte proliferation.
8. These observations suggest that, although fatty acid suppression of interleukin-2 production may play a role in the inhibition of proliferation, it is not the sole mechanism by which fatty acids act.