Neutralizing IL-15 Inhibits Pro-inflammatory Cytokine Production and Promote Protective Immune Responses

Introduction: IL-15 has been showed to have a central role in the pathogenesis of coeliac disease (CD) in the development of mucosal damage, as well as in the functional impairment of T regulatory (Treg) cells. Therefore, such cytokine appears to be a very relevant target for therapeutic intervention in CD. In this study, we investigated the effect of a neutralizing IL-15 antibody on the mucosal immune response in CD, by using organ culture system. Methods: mRNA transcripts of IFN-g and TGF-b, pro- and anti-inflammatory cytokines, respectively, were analysed by quantitative reverse transcriptase-PCR (qRT-PCR) in intestinal biopsies from active CD patients (ACD) (n 59) cultured for 24 hours in medium with or without anti-IL-15 antibody. Results: In ex vivo organ cultures of intestinal mucosa of active CD patients, anti IL-15 antibody induced a significant increase of TGF-b mRNA expression (*P, 0.05) and a trend toward a reduction of IFN-g (not statistically significative) (Figure 1). Conclusion: Our results suggest that antibody-mediated blockade of IL-15 reverse the Th1 inflammatory responses and restore Treg suppressor capacity in CD. Therefore, anti-IL-15 treatment might be considered as a novel therapy to normalize intestinal lymphocyte function in CD patients.