Fasting Prevents Experimental Murine Colitis Produced by Dextran Sulfate Sodium and Decreases Interleukin-1β and Insulin-Like Growth Factor I Messenger Ribonucleic Acid

Abstract Cytokines and insulin-like growth factors (IGFs) are involved in the induction and/or perpetuation of inflammatory bowel disease. The effect of fasting on inflammatory bowel disease was studied in a mouse experimental 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-1β (IL-1β), IGF-I, and tumor necrosis factor-α messenger RNAs (mRNAs) were quantified by Northern blot hybridization and expressed as a percentage of mRNA abundance in fed controls. In DSS mice, IL-1β 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 compared to fed DSS mice). Tumor necrosis factor-α 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-1β mRNA was localized to the lamina propria of colonic mucosa in fed DSS animals, but was not detectable in other groups. We conclude that fasting has a protective effect on the progression of acute DSS-induced colitis. This is associated with decreased expression of IL-1β and IGF-I mRNAs in the colon.