7.4 EFFECT OF MILK PEPTIDES ON TUMOR GROWTH
lactic acid bacteria, through the mechanism of fermentation, may release compounds that react with the immune system parameters and induce protective immunity against infections and some tumors.76 In vivo experiments showed that protentiation of the immune system and inhibition of tumor development is likely related the proteolysis that occurs during milk fermentation.77,78 Milk fermented with Lb. helveticus R389 increased the number of IgA+ B cells in the small intestine and bronchial tissues(Table 7.2). Increases in the levels of secretory IgA and activation of the B cells to enter the IgA cycle were not noticeable when milk was fermented by the nonproteolytic variant of this strain(Table 7.3).77
Perdigon et al. 79 suggested that the increased numbers of cells secreting IgA in the large intestine of mice given yogurt could contribute to decreasing the tissuedamaging consequences of a permanent inflammatory response, which occurs during the development of tumors and neoplasia. IgA is considered to be an immune barrier in colonic neoplasia. The increase of the mucosal immunity and the enhancement of cellular mobilization of IgA+ cells are properties that can be exploited clinically to prevent infections and development of some tumors in the mucosal network. Those results could be therapeutically used to redirect the immunologic memory and favor a response other than T helper subset 2 cell, which could prevent an allergic inflammatory disease.80 Lb. helveticus, in our laboratory, was able to hydroyze milk proteins and cause the release of peptides, as was shown by the level of proteolysis and the HPLC elution pattern of milk after fermentation(Figure 7.1). This same fermented milk increased the phagocytic index of peritoneal macrophages in mice, which was directly correlated with a regression of fibrosarcoma.77 Further in vivo studies designed to analyze the particular effect of the different peptidic fractions in milk after fermention by Lb. helveticus have led to the identification of a bioactive fraction. This fraction increased the number of IgA secreting cells in the GALT(gut-associated lymphoid tissue) and caused the regression of subcutaneously implanted fibrosarcomas, an immunodependent tumor (Figure 7.2).78 These studies