DECREASE IN SENSITIZATION RATE AND INTESTINAL ANAPHYLACTIC RESPONSE AFTER NITRIC-OXIDE SYNTHASE INHIBITION IN A FOOD HYPERSENSITIVITY MODEL

Background-Although nitric oxide (NO) has been found to have a role in gut inflammation and to modulate immunoglobulin production, little is known about its part in food hypersensitivities. Aim-This study aimed to evaluate the role of NO through the inhibition of constitutive and inducible NO synthase (cNOS and iNOS respectively) on the sensitisati on process (antibody titres) and on intestinal anaphylactic responses (colonic hypersecretion upon antigen challenge). Animals and methods-G uinea pigs sensitised to cow's milk proteins were treated either durin g the sensitisation period or before antigen challenge by N-nitro-L-ar ginine methyl ester (L-NAME) (inhibiting both cNOS and iNOS) or amino- guanidine (selective iNOS or inhibitor). Results-Chronic treatment by L-NAME or aminoguanidine reduced antibody titres and the secretory res ponse to antigen challenge. In contrast, only L-NAME administered befo re challenge was able to antagonise the hypersecretion induced by the challenge. Conclusions-NO generated by iNOS has a role in the sensitis ation process: iNOS inhibition results in lower rates of antibodies le ading to a reduced secretory response upon challenge. In contrast, blo ckade of colonic hypersecretion by L-NAME but not by aminoguanidine su ggests that NO via cNOS is a key mediator in intestinal anaphylactic r eactions.