H. Al-Hassi*1, R. Vora2, R. Durga2, M. Inés2, A. Hart3, D. Bernardo2, F. John4, S. Knight2
1Imperial College London, Immunology, London, United Kingdom, 2Imperial College London, Antigen Presentation Research Group(APRG), London, United Kingdom, 3St Mark's Hospital, Colorectal Surgery & IBD Unit, London, United Kingdom, 4Chelsea and Westminster Hospital, Paediatric Gastroenterology, London, United Kingdom
Crohn's disease (CrD) is an inflammatory bowel disease characterised by dysregulated mucosal immunity underscored by increased numbers of mature dendritic antigen-presenting cells (DC)¬¬. An early symptom of CrD is increased abdominal fat, providing a source of adipokines including leptin (pro-inflammatory) and adiponectin (anti-inflammatory). Exclusive enteral nutrition (EN) containing TGF-beta and medium-chain-triglycerides, induces remission and leads to mucosal healing in active paediatric CrD. We hypothesised that effects of EN involve immunomodulatory actions of lipids and adipokines. Our aims were therefore to investigate adipokines and lipid contents of DC in paediatric CrD before and after EN treatment.
Methods: Eight CrD children (median = 13, age 9 - 15), with PCDAI at diagnosis (median = 55, range 25 - 65), were treated with EN for 6 weeks. Blood samples were collected before and after therapy. DC were identified in peripheral blood mononuclear cells from paediatric CrD patients as a cell population positive for HLA-DR and negative for CD3, CD14, CD16, CD19, CD34 and CD56 by flow cytometry. Lipid content, maturation status, leptin, leptin receptor, adiponectin and the adiponectin receptor R2 of DC were determined.
Results: Treatment with EN induced clinical remission in all patients (PCDAI < or = 10) and improved nutritional status defined by weight gain. Leptin expression was significantly decreased in DC after EN treatment by 17% (p<0.03) and there was a trend towards a decrease in its receptor. In contrast, the expression of adiponectin and its receptor significantly increased in DC post-EN by 68% and 40% (p<0.007 and p<0.03) respectively. ILT3 expression, a surface receptor which is highly expressed on immature DC and renders them "tolerogenic", was significantly increased on DC post-EN by 55% (p<0.03). There were no significant differences in total lipid content of DC before and after treatment.
Conclusion: Beneficial actions of EN in paediatric CrD may include the inhibition of DC maturation and regulating DC activity by increasing intracellular levels of the immunosuppressive adipokine, adiponectin.