Monoclonal antibodies against tumor necrosis factor (TNF), which include infliximab, have demonstrated their usefulness in the treatment of active forms of CD. However, differences in efficacy have been observed between the various commercial brands, which all target soluble TNF with the same affinity. This indicates that neutralization of soluble TNF is not the only mechanism of action involved in the effect of these treatments.

A group of researchers in Nantes sought to elucidate the mechanisms of action of infliximab during the course of CD, and in particular, its effects upon secretion of IL-15 and its soluble receptor (sIL-I5Ra). The study, published in Gastroenterology, demonstrated that during the course of CD, expression of sIL-15Ra and the IL-15/IL-15Ra complex in serum was correlated with the inflammatory status of patients [1]. Moreover, in patients who were responders to infliximab treatment, the authors observed an increase in sIL-15Ra and the IL-15/IL-15Ra complex, leading to a decrease in the serum levels of IL-15. The direct effect of infliximab upon modulation of the IL-15/IL-15Ra system was next demonstrated in vitro in colitic epithelial cell lines.

The conclusions of this study indicate that IL-15 and its soluble receptor are implicated in the response to infliximab, which is not the case for the other two antibodies to TNF, adalinumab and etanercept, which appear to have different mechanisms of action. Quantification of IL-15 and its soluble receptor could constitute a prognostic parameter in the response to infliximab.

This study should be further expanded so as to develop prognostic tools for orienting the choice of treatment.

1. Bouchaud, G., et al., Interleukin-15 and its soluble receptor (sIL-15Ralpha) mediate the response to infliximab in patients with Crohn's disease. Gastroenterology.