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Nutritional Immunology

Dietary Curcumin and Limonin Suppress CD4⁺ T-Cell Proliferation and Interleukin-2 Production in Mice^1–3,

⁴ Program in Integrative Nutrition and Complex Diseases, ⁵ Intercollegiate Faculty of Nutrition, ⁶ Department of Veterinary Pathobiology, ⁷ Vegetable and Fruit Improvement Center, and ⁸ Center for Environmental and Rural Health, Texas A&M University, College Station, TX 77843; and ⁹ Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, TX 77843

Phytochemicals may reduce chronic inflammation and cancer risk in part by modulating T-cell nuclear factor-B (NF-B) activation. Therefore, we examined the effects of curcumin (Cur) and limonin (Lim) feeding on NF-B–dependent CD4⁺ T-cell proliferation. DO11.10 transgenic mice (n = 5–7) were fed diets containing 1% Cur or 0.02% Lim combined with either (n-6) PUFA [5% corn oil (CO)] or (n-3) PUFA [4% fish oil+1% corn oil (FO)] for 2 wk, followed by splenic CD4⁺ T-cell isolation and stimulation with ovalbumin peptide 323–339 (OVA) and antigen-presenting cells from mice fed a conventional nonpurified rodent diet. Both Cur and Lim diets suppressed (P < 0.05) NF-B p65 nuclear translocation in activated CD4⁺ T-cells. In contrast, activator protein-1 (c-Jun) and nuclear factor of activated T-cells c1 were not affected compared with the CO control diet (no Cur or Lim). CD4⁺ T-cell proliferation in response to either mitogenic anti-CD3/28 monoclonal antibodies (mAb) or antigenic stimulation by OVA was also suppressed (P < 0.05) by Cur as assessed by carboxyfluorescein succinimidyl ester staining. In contrast, interleukin-2 production was not directly associated with NF-B status. Interestingly, dietary combination with FO enhanced the suppressive effects (P < 0.05) of Cur or Lim with respect to CD4⁺ T-cell proliferation in response to anti-CD3/28 mAb. These results suggest that combination chemotherapy (FO+Cur or Lim) may favorably modulate CD4⁺ T-cell–mediated inflammation.

^* To whom correspondence should be addressed. E-mail: r-chapkin{at}tamu.edu.

Manuscript received 26 November 2008. Initial review completed 16 January 2009. Revision accepted 12 February 2009.

Published online 25 March 2009.