Elevated serum free fatty acid concentrations inhibit T lymphocyte signaling

Unbound cis-unsaturated free (i.e., nonesterified) fatty acids (FFA) inhibi t T lymphocyte activation in vitro and therefore may exert immunosuppressiv e effects. However, in blood serum the major proportion of FFA is tightly b ound to albumin, whereas unbound FFA are hardly detectable, Since serum FFA elevation occurs under pathological conditions like insulin resistance or cancer, which are often associated with a disturbed immune response, we add ressed the question of whether increased serum EFA concentrations could aff ect T lymphocyte activation under in vivo conditions. Our studies revealed that 1) addition of pure long-chain cis-unsaturated EFA in the absence of a lbumin inhibited calcium response in cultured Jurkat T cells. 2) In healthy volunteers, serum FFA elevation by a lipid/heparin infusion, including pre dominantly unsaturated fatty acids, decreased calcium response of cultured T cells in contrast to studies without heparin, 3) Most notably, stepwise i ncreasing serum FFA by lipid/heparin infusion also inhibited calcium respon se of simultaneously isolated autologous peripheral blood T lymphocytes as well as their CD4(+) and CD8(+) subsets. In conclusion, our data emphasize that serum EEA elevation is able to exert immunosuppressive effects in vivo .