Diclofenac enhances allergic responses in a mouse peanut allergy model
Article first published online: 16 AUG 2010
© 2010 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 41, Issue 3, pages 424–433, March 2011
How to Cite
Bol-Schoenmakers, M., Bleumink, R., Marcondes Rezende, M., Mouser, E., Hassing, I., Ludwig, I., Smit, J. J. and Pieters, R. H. H. (2011), Diclofenac enhances allergic responses in a mouse peanut allergy model. Clinical & Experimental Allergy, 41: 424–433. doi: 10.1111/j.1365-2222.2010.03594.x
- Issue published online: 7 FEB 2011
- Article first published online: 16 AUG 2010
- Submitted 22 October 2009; revised 11 June 2010; accepted 6 July 2010
- mouse allergy model;
- non-steriodal anti-inflammatory drugs;
- oral tolerance;
- peanut allergy
Cite this as: M. Bol-Schoenmakers, R. Bleumink, M. Marcondes Rezende, E. Mouser, I. Hassing, I. Ludwig, J. J. Smit and R. H. H. Pieters, Clinical & Experimental Allergy, 2011 (41) 424–433.
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.