This week on TIBDI: we learn why NLRP3 polymorphisms are interesting for Crohn’s disease, and the combination treatment of anti-TNFα and methotrexate isn’t better than anti-TNFα alone.
NLRP3: Key to Protection from Intestinal Infection?
NLRP3 is an intracellular receptor geared for the recognition of bacteria and is associated with Crohn’s disease (CD) susceptibility. It’s known to be important for causing the formation of inflammasomes, which are needed for the production of pro-inflammatory IL-1β and IL-18. Using the intestinal pathogen Citrobacter rodentium, scientists from the University of Oxford, have now shown this process in action in mice. They found that without the NLRP3-induced inflammasomes, the pathogenic bacteria could easily colonize the intestines and cause severe intestinal inflammation. This would suggest that NLRP3 triggers an early defense against bacterial invasion, preventing widespread inflammation. This may explain why polymorphisms of NLRP3 are associated with CD.
Anti-TNFα Needs No Help
One strategy for treating CD that is resistant to medication is to double-up and combine different kinds of medications. One option, the combination of anti-TNFα and methotrexate, has already proved useful for arthritis patients. Therefore, it was tested in CD patients. In a 50-week clinical trial with 126 CD patients, patients were brought into remission with prednisone and maintained with anti-TNFα, with or without methotrexate. After the treatment period, the combination treatment proved no more successful than anti-TNFα alone.
- Feagan, B. G., McDonald, J. W. D., Panaccione, R., Enns, R. A., Bernstein, C. N., Ponich, T. P., et al. (2013). Methotrexate in Combination with Infliximab is no More Effective than Infliximab Alone in Patients with Crohn’s Disease, Gastroenterology, 1–33. doi:10.1053/j.gastro.2013.11.024
- Song-Zhao, G. X., Srinivasan, N., Pott, J., Baban, D., Frankel, G., & Maloy, K. J. (2013). Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen, Mucosal Immunology, 1–12. doi:10.1038/mi.2013.94