No abstract

The effects of dietary curcumin on three major types of immune function were examined in rats. Antibody (IgG) production, delayed-type hypersensitivity and natural killer cell activity were evaluated after 5 weeks of dietary exposure to 1, 20 or 40 mg/kg curcumin. The highest dose of curcumin significantly enhanced IgG levels. Rats receiving lower dietary concentrations (1 or 20 mg/kg) of curcumin were not different in IgG production from rats receiving no curcumin in their diet. Neither delayed-type hypersensitivity nor natural killer cell activity was different from control values at any dietary concentration of curcumin. In vitro incubation of YAC-1 and EL4 tumor cells and normal splenocytes in varying concentrations of curcumin for varying times revealed differences between cell types in curcumin's effects on cell proliferation and viability. No cytotoxic effect was seen in EL4 cells at 125 micrograms/ml curcumin at 4, 24 and 48 hrs incubations, however, cell proliferation was reduced by almost 50% at 24 hrs. YAC-1 cell viability and cell numbers were diminished at longer incubations. A lower curcumin concentration (1.25 micrograms/ml) enhanced cell growth in the YAC-1 cells at 24 and 48 hr. This enhancement was not seen in spleen or EL4 cells.

Rats fed 100 mg/kg quercetin (QUE) daily for 7 weeks had significantly enhanced natural killer cell activity compared to their vehicle (VEH)-fed control. In contrast, rats fed 100 mg/kg QUE and treated with the colon carcinogen, azoxymethane had significantly reduced natural killer cell activity compared to their VEH-fed azoxymethane-treated control. There was no significant difference in natural killer cell activity between the two control groups. Antibody production and delayed-type hypersensitivity were not altered by QUE feeding in any treatment group. In vitro exposure of splenic natural killer cells to 1mM QUE significantly decreased natural killer cell cytotoxicity. Lower QUE concentrations produced a non-significant reduction in natural killer cell activity that was restored to control values at 1 x 10(-13)M QUE. The distribution, multiplicity and total number of colonic preneoplastic lesions, aberrant crypt foci, was not significantly different in the QUE-fed azoxymethane-treated rats when compared to azoxymethane-treated vehicle-fed rats at the conclusion of 7 week feeding period. We found no correlation between immune function and development of preneoplastic colon lesions in this study.

This study was designed to investigate possible additive or synergistic action among sphingomyelin (SPH), cis-9,trans-11-conjugated linoleic acid (CLA), and butyrate (BTY) against colon cancer and modulation of immune functions in vivo in male Sprague-Dawley rats. Each of the 5 groups of rats was fed either 35 mg SPH, 100 mg CLA, or 100 mg BTY/kg body weight, a combination of the 3 compounds at the same doses, or none of the compounds, for 7 wk. Rats were injected with azoxymethane, a colon carcinogen, to induce the formation of aberrant crypt foci, preneoplastic lesions of colon cancer. Parameters measured included number and multiplicity (number of crypts per focus) of aberrant crypts, immune functions such as innate immunity (natural killer cell cytotoxicity), humoral immunity (development of antibodies), and cell-mediated immunity (delayed-type hypersensitivity). Results show that the groups treated with SPH, CLA, and BTY individually had significantly higher natural killer cell (NK) cytotoxicity than the group treated with all compounds. The CLA group also had significantly higher NK activity than the control group. This study shows that the three compounds may not act additively or synergistically either to inhibit the development of aberrant crypts or to enhance immune functions. In fact, exposure to the combined compounds may be antagonistic to enhancement of NK function by the individual chemicals.