Pharmacological concentrations of lipid emulsions inhibit interleukin-2-dependent lymphocyte responses in vitro

Most immunological functions are accomplished by means of interactions between mediator molecules (cytokines or lymphokines) and their specific receptors on the lymphocyte surface. One particular lymphokine, Interleukin-2 (IL-2) is central to the generation of most immune responses including those with antitumor activity. Prompted by two clinical trials which have suggested distinct but apparently opposite effects of lipid emulsions on the production of and lymphocyte responses to IL-2 we have examined the effects of pharmacological concentrations of three lipid emulsions currently in clinical use on IL-2 related interactions in vitro. Mitogen-stimulated and IL-2 activated human lymphocyte proliferation were both inhibited in a dose-dependent manner in the presence of all three lipid emulsions although the effects were less marked with the solution in which 50% of the calories are present as medium-chain triglycerides (MCT) rather than long-chain triglycerides (LCT). Similarly the LCT, but less so the MCT-containing solutions inhibited the generation of cytotoxic lymphokine-activated killer cells. These solutions did not inhibit the proliferation of cell lines which are not growth-factor dependent but did inhibit the growth of an IL-2-dependent cell line. We conclude that lipid emulsions can upset IL-2-dependent lymphocyte responses. These observations may lead to parenteral feeding regimens which are less immunocompromising for the tumor-bearing patient.