DECREASE IN SYSTEMIC TOLERANCE TO FED OVALBUMIN IN INDOMETHACIN-TREATED MICE

The oral administration of non-steroidal anti-inflammatory drugs (NSAI D) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leadin g to the inflammatory lesions are hypothetical. The increased intestin al permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin- treated mice and the increase was proportional to the dose of indometh acin. It was associated with epithelial and subepithelial lesions. Mor eover, the systemic humoral and, to a lesser extent, the cellular tole rance were partially abrogated in the treated mice. These findings sug gest that the oral administration of indomethacin in mice induces an i ncreased passage of fed antigen through the intestinal epithelium asso ciated with a decrease in systemic tolerance to this antigen. The reas on for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the int estinal epithelial cells and a direct immunomodulating effect of indom ethacin may also be involved. This decrease in systemic tolerance to l uminal antigen could be involved in the development of NSAID enteropat hy.