Unsaturated fatty acids inhibit IL-2 production in thymus-dependent antibody responses in vitro.

Albumin-complexed unsaturated fatty acids such as oleic acid (18:1) exerted a dose-dependent inhibitory effect on in vitro primary anti-TNP plaque-forming cell (PFC) responses to trinitrophenyl keyhole limpet haemocyanin (TNP-KLH), but did not affect primary PFC responses to trinitrophenyl lipopolysaccharide (TNP-LPS). The addition of 150 microM 18:1 at the initiation of thymus-dependent (T-D) antibody cultures inhibited the subsequent PFC response by 85%, and removal of the fatty acid after 24 hr did not reverse its inhibitory effect. By contrast, delaying the addition of 18:1 until 3 or 4 days after culture initiation abrogated its inhibitory effects. T-D antibody cultures displayed maximum production of interleukin-2 (IL-2) on the third day after culture initiation and a 24-hr exposure to 18:1 resulted in a dose-dependent inhibition of IL-2 production. Lastly, the addition of exogenous IL-2 reversed the inhibition of PFC responses in cultures transiently exposed to 18:1. These findings suggest that unsaturated fatty acids inhibit in vitro T-D PFC responses by selectively interfering with early stages of the antibody response, particularly those events leading to IL-2 production by T-helper cells.