Diclofenac enhances allergic responses in a mouse peanut allergy model.
BACKGROUND
Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) interfere with cyclo-oxygenase-mediated synthesis of prostaglandins, resulting in the inhibition of inflammatory immune responses. In contrast, it is known that NSAIDs are able to induce gastrointestinal damage.


OBJECTIVE
Our aim was to investigate whether NSAIDs are able to enhance sensitization or abrogate tolerance to food antigens.


METHODS
Mice were exposed to diclofenac and sensitized to peanut using cholera toxin as a mucosal adjuvant. In a tolerance model, oral tolerance was induced via feeding of peanut 3 weeks before sensitization with peanut. Diclofenac was administered before peanut feeding. After 4 weeks, peanut-specific antibodies in the serum and cytokine production in the spleen were measured. Induction of intestinal damage after oral exposure with diclofenac and peanut + cholera toxin was examined microscopically.


RESULTS
Diclofenac-exposed animals showed increased levels of peanut-specific IgG1, IgG2a and IgE in the serum compared with vehicle-treated animals. Furthermore, peanut-induced cytokine production in the spleen was elevated upon diclofenac treatment. Importantly, diclofenac did not induce peanut-allergic responses in the absence of the cholera toxin, although exposure to diclofenac and peanut + cholera toxin resulted in intestinal epithelial damage. Reduced peanut-specific antibody production in the case of oral tolerance was not reversed after diclofenac exposure. However, oral tolerance, as measured by inhibition of peanut-specific cytokine responses, was reverted by diclofenac.


CONCLUSIONS
These data point towards an increased risk for induction of food-allergic responses by diclofenac, when other circumstances are also in favour of induction of allergy.
Bol-Schoenmakers
M
M
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. m.bol-schoenmakers@uu.nl
Bleumink
R
R
Marcondes Rezende
M
M
Mouser
E
E
Hassing
I
I
Ludwig
I
I
Smit
J J
JJ
Pieters
R H H
RH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D021183:Peanut Hypersensitivity / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac