Decrease in sensitisation 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.


OBJECTIVE
This study aimed to evaluate the role of NO through the inhibition of constitutive and inducible NO synthase (cNOS and iNOS respectively) on the sensitisation process (antibody titres) and on intestinal anaphylactic responses (colonic hypersecretion upon antigen challenge).


METHODS
Guinea pigs sensitised to cow's milk proteins were treated either during the sensitisation period or before antigen challenge by N-nitro-L-arginine methyl ester (L-NAME) (inhibiting both cNOS and iNOS) or amino-guanidine (selective iNOS inhibitor).


RESULTS
Chronic treatment by L-NAME or aminoguanidine reduced antibody titres and the secretory response to antigen challenge. In contrast, only L-NAME administered before challenge was able to antagonise the hypersecretion induced by the challenge.


CONCLUSIONS
NO generated by iNOS has a role in the sensitisation process: iNOS inhibition results in lower rates of antibodies leading to a reduced secretory response upon challenge. In contrast, blockade of colonic hypersecretion by L-NAME but not by aminoguanidine suggests that NO via cNOS is a key mediator in intestinal anaphylactic reactions.
Fargeas
M J
MJ
Department of Pharmacology-Toxicology, Institut National de la Recherche Agronomique, Toulouse, France.
Theodorou
V
V
Weirich
B
B
Fioramonti
J
J
Buéno
L
L
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis; D007073:Immunoglobulin E / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007782:Lactoglobulins / Q000494:pharmacology; D008297:Male; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010539:Permeability
D007070:Immunoglobulin A; D007782:Lactoglobulins; D009569:Nitric Oxide; D007073:Immunoglobulin E; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester