FASTING PREVENTS EXPERIMENTAL MURINE COLITIS PRODUCED BY DEXTRAN SULFATE SODIUM AND DECREASES INTERLEUKIN-1-BETA AND INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RIBONUCLEIC-ACID

Cytokines and insulin-like growth factors (IGFs) are involved in the i nduction and/or perpetuation of inflammatory bowel disease. The effect of fasting on inflammatory bowel disease was studied in a mouse exper imental model of acute colitis caused by adding dextran sulfate sodium (DSS) to drinking water. Animals were either fed ad libitum or fasted (water only) for 2 days before death. Inflammation and tissue damage, measured as a colitis activity score, were markedly reduced in fasted (2.4 +/- 0.1) compared to fed (5.3 +/- 0.1) DSS animals (P < 0.0001). Colon interleukin-1 beta (IL-1 beta), IGF-I, and tumor necrosis facto r-ct messenger RNAs (mRNAs) were quantified by Northern blot hybridiza tion and expressed as a percentage of mRNA abundance fed controls. In DSS mice, IL-1 beta mRNA was elevated in the fed group (954 +/- 155%; P < 0.001), but was suppressed in fasted animals (71.1 +/- 11%). IGF-I mRNA also was elevated in fed DSS mice (421 +/- 71%; P < 0.01). This increase was attenuated in fasted DSS mice (202 +/- 17%; P < 0.01 comp ared to fed DSS mice). Tumor necrosis factor-ru mRNA was increased in fed DSS mice (162 +/- 15%; P < 0.01), but was not significantly lower in fasted animals. By in situ. hybridization, IL-1 beta mRNA was local ized to the lamina propria of colonic mucosa in fed DSS animals, but w as not detectable in other groups. We conclude that fasting has a prot ective effect on the progression of acute DSS-induced colitis. This is associated with decreased expression of IL-1 beta and IGF-I mRNAs in the colon.