Comparison of iron-reduced and iron-supplemented semisynthetic diets in T cell transfer colitis.

Clinical observations in inflammatory bowel disease patients and experimental studies in rodents suggest that iron in the intestinal lumen derived from iron-rich food or oral iron supplementation could exacerbate inflammation and that iron depletion from the diet could be protective. To test the hypothesis that dietary iron reduction is protective against colitis development, the impact of iron reduction in the diet below 10 mg/kg on the course of CD4+ CD62L+ T cell transfer colitis was investigated in adult C57BL/6 mice. Weight loss as well as clinical and histological signs of inflammation were comparable between mice pretreated with semisynthetic diets with either < 10mg/kg iron content or supplemented with 180 mg/kg iron in the form of ferrous sulfate or hemin. Accumulation and activation of Ly6Chigh monocytes, changes in dendritic cell subset composition and induction of proinflammatory Th1/Th17 cells in the inflamed colon were not affected by the iron content of the diets. Thus, dietary iron reduction did not protect adult mice against severe intestinal inflammation in T cell transfer induced colitis.

Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse.

Polysaccharide (PLP) isolated from Phellinus linteus inhibits tumor growth and metastasis by enhancing immune functions of macrophages, dendritic cells, NK cells, T cells, and B cells. Here, we report that PLP can inhibit the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Although 80% of the NOD mice had developed diabetes by 24 weeks of age, none of the PLP-treated NOD mice developed diabetes. The mean blood glucose levels were 110mg/dl in PLP-treated mice and 499mg/dl in control NOD mice. Histological examination of the pancreatic islets revealed that most of the islets isolated from PLP-treated mice were less infiltrated with lymphocytes compared with those of control mice. Spleen cells from diabetic NOD mice could adaptively transfer diabetes into NOD/SCID mice, but those from PLP-treated NOD mice showed delayed transfer of diabetes. PLP inhibited the expression of inflammatory cytokines, including IFN-gamma, IL-2, and TNF-alpha by Th1 cells and macrophages, but up-regulated IL-4 expression by Th2 cells in NOD mice. PLP did not prevent streptozotocin-induced diabetic development in ICR mice. Taken together, these results suggest that PLP inhibits the development of autoimmune diabetes by regulating cytokine expression.

A key role for prostaglandin I2 in limiting lung mucosal Th2, but not Th1, responses to inhaled allergen.

The cellular events that serve to regulate lung mucosal Th2 responses and limit allergic inflammatory reactions are unclear. Using the DO11.10 TCR transgenic mouse, we developed a model of T cell-mediated pulmonary inflammation and demonstrated that high levels of PGI(2) are produced in the airways following OVA inhalation. Selective inhibition of cyclooxygenase-2 in vivo specifically reduced PGI(2) synthesis and resulted in a marked increase in Th2-mediated, but not Th1-mediated, lung inflammation. The elevated Th2-mediated inflammatory response elicited by the cyclooxygenase-2 inhibitor was associated with enhanced airway hyperreactivity and was coincident with a marked increase in the levels of IL-4, IL-5, and IL-13 in the airways, but a reduction in IL-10 production. In keeping with these observations, we found that the mRNA for the PGI(2) receptor was expressed by Th2, but not Th1, cells, and transcripts for the PGI(2) receptor were induced by IL-4 and OVA peptide stimulation. Interestingly, treatment with PGI(2) or its stable analog, carbaprostacyclin, augmented IL-10 production by Th2 cells. Collectively, our findings reveal a key role for PGI(2) in differentially limiting Th2 responses, possibly by promoting production of the immunosuppressive cytokine IL-10 at the site of allergic lung inflammation. These results indicate an important role for prostanoids generated during inflammation in regulating mucosal T cell responses and highlight a potential risk in the use of cyclooxygenase-2-specific inhibitors by allergic asthmatics.