Protective effect of lactate against TNBS-induced colitis in a murine model

IRAPORDA, C; ROMANIN, D; MULET, AP; ABRAHAM, AG; GARROTE, G; RUMBO, M

Buenos Aires

Congreso; IV Congress of LASID; 2015

Sociedad Latinoamericana de Inmunodeficiencias (LASID)

We have previously shown that lactate can regulate critical functions of several key players of the immune system such as macrophages and dendritic cells, also being able to modulate inflammatory activation of epithelial cells. In order to link the in vitro immunomodulation capacity of lactate to the in vivo effect, we evaluated the potential to protect mice from colitis induced by TNBS. There were used 20 SPF, Balb/C mouses, six-weeks old. Lactate 200 mM was administered by intrarectal instillation of 200 µl, meanwhile control groups received 200 µl of PBS. Experimental colitis was induced 2 h later, by intrarectal instillation of 0.5 mg of TNBS in 50% ethanol or 50% ethanol solution to control groups. Animals were sacrificed after 48 h. No significant variation in weight and no signs of inflammation were observed in vehicle groups. We compared the development of colitis in mice either pre-treated or not with lactate. Characteristic features of colitis, colonic inflammation with several epithelial damage were observed in PBS-treated group, leading to an inflammation score of 4.67 ±2.34, and high concentration of serum IL-6. In contrast, group pre-treated with lactate showed lower colonic inflammation and a score of 1.40 ±0.54 (p<0.05) with lower levels of serum IL-6 (p<0.05). A minor weight loss was also observed in animals pre-treated with lactate. In conclusion, increase in lactate concentration in colon results protective for TNBS-induced colitis. These suggest that lactate could be a potential beneficial microbiota metabolite and may contribute to health promoting-properties on the intestinal mucosa.