Milk casein-based diet containing TGF-beta controls the inflammatory reaction in the HLA-B27 transgenic rat model.

BACKGROUND: A casein-based formula containing TGF-beta has been successfully used in adolescents during acute episodes of Crohn's disease. The role played by this molecule requires confirmation. We have examined the capacity of a TGF-beta containing diet to control the intestinal inflammation in HLA-B27 transgenic rats, and compared its effects with a similar diet devoid of TGF-beta. METHODS: Three groups of rats were studied. HLA-B27/hbeta2M transgenic rats were fed with a casein-based rat-adapted diet containing TGF-beta or a control casein-based diet without TGF-beta. Fischer control animals were fed the latter. Body weight, dietary intake, tissue weights, fecal samples, leukocyte counts, and acute phase response were analyzed. Intestinal inflammation was assessed by histology, myeloperoxidase, and mRNA expression of cytokines. MUC2 protein expression was assessed by immunohistochemistry. Breakdown of muscle protein was examined. RESULTS: The test diet improved diarrhea increasing the fecal dry matter and the colonic inflammation as shown by a lower inflammatory score (2.43 +/- 1.13 vs 4.42 +/- 0.53, p < .05), lower mucosal thickness (431.25 +/- 72.29 vs 508.57 +/- 81.32 microm, p = .08) and decreased IFNgamma mRNA expression. MUC2 protein expression was increased in HLA rats fed the TGF-beta diet compared with HLA rats fed the control diet, but restitution to normal pattern was not observed. The test diet also decreased leukocytosis and the acute phase response and improved the muscle catabolic response. CONCLUSION: The TGF-beta containing diet has a beneficial effect in an animal model of intestinal inflammation. Our observations support a potential role for dietary TGF-beta in the restoration of immune homeostasis.

The inflammatory response to vaccination is altered in the elderly.

To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and acute phase proteins were analysed before and 2 days after vaccination. Prior to vaccination, only IFN-gamma production was lower in the elderly than in the young subjects due to a lower mononuclear cell number. In the same time, although in the normal range, several acute phase proteins were greater in elderly than in young subjects, suggesting a low-grade inflammatory state in the elderly. After vaccination, IFN-gamma production remained lower in the elderly than in the young, supporting an altered cell-mediated immunity with advancing age. TNF-alpha production was unaffected by either ageing or vaccination. IL-6 production was stimulated by vaccination in young subjects but not significantly in the elderly. IL-10 production was inhibited by vaccination in the elderly but not in the young. Acute phase proteins were less increased in elderly than in young subjects. Taken together, these results support a general lack of inflammatory response in the elderly exposed to an immune challenge and suggest that immune deficiency may concern both Th1 and Th2 responses. However, the interpretation must respect the limitation of small subjects number.

Increased tissue protein synthesis during spontaneous inflammatory bowel disease in HLA-B27 rats.

Inflammatory bowel diseases (IBDs) are associated with an increased whole-body protein turnover. In certain drug-induced experimental models of IBD, disturbances of protein synthesis in tissues have been reported recently, but it is unclear if similar disturbances occur in other chronic intestinal diseases. Therefore we investigated changes in protein synthesis in different tissues of HLA-B27 (human leucocyte antigen B27) transgenic rats that develop spontaneously chronic inflammation, with major involvement of the colon. Protein synthesis rate in HLA-B27 rats was shown to be higher in nine different tissues compared with control (Fisher 344) rats. The absolute rate of protein synthesis was highly stimulated at the main inflammatory site (+290% in the colon). However, liver, muscle and skin appeared to be major contributors to the increased protein synthesis observed at the whole-body level. Despite the increased protein synthesis, HLA-B27 rats presented a marked atrophy of muscles, which suggests an increased proteolysis. These results contrast with metabolic disturbances described in acute inflammation and colitis induced by drugs (i.e. dextran sodium sulphate). The present study suggests that the modifications of protein metabolism are strongly influenced by the type of the inflammatory diseases and thus by the underlying mechanisms, which result in different metabolic adaptations and specific nutritional requirements.