Ginger compounds, especially shogaols, strongly stimulate TRPA1-mediated adrenomedullin release in normal rats while hydroxysanshools, from Japanese pepper, have a similar but weaker effect in normal rodents. In the ischemic intestine, the effect of hydroxysanshools is greater in the diseased portions of intestine while shogaols are not as effective in the ischemic intestine. To extend our understanding of TU-100��s anti-inflammatory effects, we investigated the actions of TU-100 in a model of Tcell mediated inflammation. In contrast to the TNBS- and CD4 + CD45RBhigh adoptive transfer models, activation of CD3 + T cells in mice with anti-CD3 monoclonal antibody results predominantly in small bowel inflammation. This was originally observed in humans treated with an anti- CD3 antibody to suppress organ transplant rejection. These patients developed a systemic cytokine response. Intraperitoneal injection of anti-CD3 antibody in mice appears to selectively activate small intestinal CD3 + T-lymphocytes and cause rapid pooling of intestinal contents within 1�C3 hours. This is followed by apoptosis of villus epithelial cells within 1.5�C3 hours and induction of crypt epithelial cell apoptosis within 24 hours. Anti-CD3 antibody also increases TNFa levels in the small intestinal mucosa, an effect that appears essential to the development of enteritis, as anti-CD3 antibody treatment does not increase enteropooling or cause diarrhea in the TNFa receptor knockout mouse. The present studies show TU-100 pre-treatment blocks jejunal enteropooling stimulated by anti-CD3 antibody, villus shortening, and subsequent development of enterocyte apoptosis. TU-100 also inhibits the induction of TNFa by anti-CD3 antibody. Notably, enteritis induced by anti-CD3 antibody is comparable in germ-free mice and their specific pathogen free counterparts. Treatment with either TU-100 or the ginger component block anti-CD3 antibody-induced enteritis in GF mice, indicating that their effects in this model are independent of gut SMANT hydrochloride microbes. Anti-CD3 antibody treatment induces a unique type of acute enteritis that is dependent on T cells and specifically appears to be RU 28318, potassium salt regulated by lamina propria CD3 + CD4 + lymphocytes. The present study demonstrates for the first time that anti-CD3 antibody induced enteritis also occurs in germ free mice. Therefore this intestinal inflammation is microbe-independent, unlike other models of colitis such as CD45RBhi cell adoptive transfer, piroxicam treatment in mice, or the HLA B27 rat colitis.