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INFLAMMATION/IMMUNITY/MEDIATORS

Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection

¹Department of Pediatrics, Steele Children's Research Center, and ²Department of Immunobiology, University of Arizona Health Sciences Center, Tucson, Arizona; and ³Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina

Submitted 6 June 2008 ; accepted in final form 17 September 2008

Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-B. Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune models of CD has not been evaluated. Therefore, we investigated the effects of dietary curcumin (0.1–1%) on the development of colitis, immune activation, and in vivo NF-B activity in germ-free IL-10^–/– or IL-10^–/–;NF-B^EGFP mice colonized with specific pathogen-free microflora. Proximal and distal colon morphology showed a mild protective effect of curcumin only at 0.1%. Colonic IFN- and IL-12/23p40 mRNA expression followed similar pattern (50% inhibition at 0.1%). Secretion of IL-12/23p40 and IFN- by colonic explants and mesenteric lymph node cells was elevated in IL-10^–/– mice and was not decreased by dietary curcumin. Surprisingly, activation of NF-B in IL-10^–/– mice (phospho-NF-Bp65) or in IL-10^–/–;NF-B^EGFP mice (whole organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore, we demonstrate that IL-10 and curcumin act synergistically to downregulate NF-B activity in IEC and IL-12/23p40 production by splenocytes and dendritic cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1 mediated colitis in IL-10^–/– mice, with moderately improved colonic morphology, but with no significant effect on pathogenic T cell responses and in situ NF-B activity. In vitro studies suggest that the protective effects of curcumin are IL-10 dependent.

inflammatory bowel disease; Crohn's disease; NF-B