Immunopotentiation of NKT cells by low-protein diet and the suppressive effect on tumor metastasis

Cell Immunol. 2004 Sep-Oct;231(1-2):96-102. doi: 10.1016/j.cellimm.2004.12.005. Epub 2005 Jan 20.

Abstract

Mice were fed with a 5% low-protein diet for two weeks, at which point tumor inoculation was conducted. Following this inoculation, the 5% low-protein diet was continued. On the other hand, control mice were fed with a normal diet (25% protein) and such diet was continued after tumor inoculation. In comparison with control mice, mice fed with the 5% low-protein diet showed a prominent prolongation of survival rate when injected with both EL4 and 3LL tumors. Interestingly, CD1d(-/-) mice, which primarily lack natural killer T (NKT) cells, did not show the prolongation of survival rate even when they received a 5% low-protein diet. The most striking phenomenon seen in tumor-bearing mice fed with the 5% low-protein diet was the suppression of tumor metastasis to the liver and lung. Such suppression was not seen in CD1d(-/-) mice who were fed with a 5% low-protein diet. Phenotypic study revealed that the proportion of NKT cells after tumor inoculation decreased in the mice fed with a normal diet. However, such decrease did not occur in mice fed with the 5% low-protein diet. Reflecting the activation of NKT cells by feeding, tumor cytotoxicity and cytokine production were also augmented by the 5% low-protein diet. These results suggest that a low-protein diet has the potential to augment the innate immunity against tumors, especially mediated by the activation of NKT cells.

MeSH terms

  • Animals
  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism
  • Antigens, CD1d
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / drug effects
  • Diet, Protein-Restricted*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology*
  • Liver / immunology
  • Liver Neoplasms / diet therapy
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / diet therapy
  • Lung Neoplasms / secondary*
  • Mice
  • Mice, Knockout
  • Neoplasm Metastasis / therapy
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Rate
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma