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Pharmacological concentrations of lipid emulsions inhibit interleukin-2-dependent lymphocyte responses in vitro
P C Sedman1, C W Ramsden, T G Brennan
1University Department of Surgery, St. James's Hospital, Leeds, England.
Insights
Lipid emulsions can impair Interleukin-2 (IL-2) dependent immune responses, affecting lymphocyte proliferation and cytotoxic cell generation. This suggests optimizing parenteral nutrition to reduce immune compromise in cancer patients.
Area of Science:
- Immunology
- Cell Biology
- Nutritional Science
Background:
- Immune responses rely on cytokine-lymphokine interactions with lymphocyte receptors.
- Interleukin-2 (IL-2) is crucial for immune responses, including antitumor activity.
- Clinical trials suggest varied effects of lipid emulsions on IL-2 production and response.
Purpose of the Study:
- To investigate the in vitro effects of three clinical lipid emulsions on IL-2 related interactions.
- To determine the impact of lipid emulsions on lymphocyte proliferation and IL-2 dependent cell growth.
Main Methods:
- Examined effects of pharmacological concentrations of three lipid emulsions on human lymphocytes and cell lines.
- Assessed mitogen-stimulated and IL-2 activated lymphocyte proliferation.
- Evaluated the generation of lymphokine-activated killer (LAK) cells.
- Tested effects on IL-2 dependent and independent cell lines.
Main Results:
- All three lipid emulsions dose-dependently inhibited lymphocyte proliferation.
- Long-chain triglyceride (LCT) emulsions showed greater inhibition than medium-chain triglyceride (MCT) emulsions.
- LCT emulsions, and to a lesser extent MCT emulsions, inhibited cytotoxic LAK cell generation.
- Lipid emulsions inhibited IL-2 dependent cell line growth but not that of independent cell lines.
Conclusions:
- Lipid emulsions can disrupt IL-2 dependent lymphocyte functions.
- Findings suggest potential for developing less immunocompromising parenteral feeding strategies for cancer patients.
Abstract:
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.
