Natural and immune anti-tumor interleukin production and lymphocyte cytotoxicity during the course of dietary protein deficiency or excess

Abstract

Dietary protein levels appear to influence tumor growth and immune responses. To determine the effect of various dietary protein levels upon natural anti-tumor immune responses, tumor growth, and acquired anti-tumor immune responses, 1 million methylcholanthrene induced (MethA) tumor cells were injected intraperitoneally (IP) into CB6F1 mice fed 4% casein (4C), 20% casein (20C), or 30% casein (30C) diets. In non-injected mice or injected CB6F1 mice on day 4, 7 and 14 following tumor challenge, the following variables were quantified: MethA cells in the peritoneal cavity, splenic natural anti-tumor cytotoxicity (NC) or acquired anti-tumor cytolytic T lymphocyte (CTL) activity, in addition to IL2 and IL3 producton by splenic lymphocytes in response to BALB/c-derived MethA cells or normal BALB/c splenic lymphocytes. IP growth of MethA was lower in 4C diet-fed mice compared with 20C- and 30C diet-fed on days 7 and 14 after tumor injection. Dietary protein level was a significant factor in anti-MethA NC and CTL. In uninjected mice, slower tumor growth in 4C diet-fed mice was associated with higher NC compared with that of 20C- and 30C diet-fed mice. However, development of CTL in 4C diet-fed mice lagged behind that of 20C- and 30C diet-fed mice on day 7 after tumor injection. Dietary protein level was a significant factor in production of IL3 by lymphocytes in the presence of MethA. Lymphocytes of mice fed diet 4C produced more MethA-induced IL3 compared with lymphocytes from mice fed diets 20C or 30C. Following tumor challenge, lympyocyte IL2 and IL3 production in the presence of MethA, but not in the presence of normal BALB/c splenic lymphocytes, were reduced in all dietary groups compared with anti-MethA IL production from splenic lymphocytes of uninjected mice. These results indicate that moderately low dietary protein levels, compared with higher levels, favorably influences early tumor grwoth due to enhanced NC and lymphocyte anti-tumor IL3 production. However, higher levels of dietary protein favorably influence the development of acquired anti-tumor CTL.