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P080. Effect of insulin like growth factor-1 on experimental colitis

D. Cano-Martínez1, L. Sebastián Monasor1, I.D. Román1, M.D. Fernández-Moreno1, B. Hernández-Breijo1, M.V.T. Lobo2, P. Sanmartín-Salinas1, J.P. Gisbert3, L.G. Guijarro1, 1Universidad de Alcalá de Henares and CIBEREHD, Biochemistry and Molecular Biology, Alcalá de Henares, Spain, 2Universidad de Alcalá de Henares IRYCIS, Cell Biology and Genetics, Alcalá de Henares, Spain, 3Hospital Universitario de la Princesa-IP, Gastroenterology and CIBEREHD, Madrid, Spain

Background

The involvement of insulin like growth factor-1-receptor (IGF-1R) in the ethiopathogenesis of inflammatory bowel disease IBD has been suggested, but there is no direct evidence due to the fact that IGF-1R knockout mice die at birth of respiratory failure. Conflicting results on the subject have been observed in IBD and in experimental models. Levels of IGF-1 in blood are low in patients with ulcerative colitis and Crohn's disease as well as in the experimental models of colitis. However the expression of IGF-1 receptor is upregulated in the colon of patients with ulcerative colitis. All these data suggest that during colitis there is a decrease in IGF-1 together with an increase in the sensitivity to the hormone. Therefore, this hormone could be useful for IBD treatment. Our aim was to study the effect of IGF-1 on body weight, mineral content, lean and fat mass, mucosal integrity, and the apoptosis of colonic cells in rats with colitis.

Methods

Colitis was induced by oral administration of 5% DSS (dextran sulphate sodium) to rats (n = 12) and a group of these animals was also treated with IGF-1 (100 µg/kg/day/i.p.). We evaluated IGF-1 effect on: i) anatomical signs (total weight, colon length, and body composition using DXA); ii) colonic mucosal integrity (by PAS-staining, Periodic Acid Schiff) and their apoptotic status (by Tunel and by western blot of caspase-3, PARP, bax and bcl-2); iii) serum biochemical parameters.

Results

Rats treated with DSS displayed pathologic signs of colitis, such as, body weight loss, diarrhea, blood in feces, shortening of colon length and decrease in serum glucose. All these changes correlated with the decrease of mineral content and lean and fat mass. However, the treatment with IGF-1 during 9 days produced a restoration of body weight and of lean mass without reversion of mineral content or fat mass. This indicates that the tissue that responds better and/or faster to IGF-1 is the muscle. Moreover, in rats with colitis there was a significant reduction of colon length that was partially reversed by IGF-1 treatment. The anatomical changes in colon during colitis were accompanied by loss of mucus production and cellular apoptosis which was partially reversed by IGF-1 treatment. However, no effect of IGF-1 on diarrhea and blood in feces was observed.

Conclusion

The present results demonstrate that IGF-1 ameliorates some symptoms of DSS-induced colitis, and therefore could be useful in IBD treatment.