A functional interleukin-10 mutation in Dutch patients with Crohn's disease

Background and aims. Interleukin-10 is an anti-inflammatory and immunomodulatory cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis. Administration of recombinant human interleukin-10 has been proposed to have a beneficial effect in a subgroup of patients with Crohn's disease. Recently, we found an interleukin-10 Glyl5Arg mutation in a family with Crohn's disease which is associated with reduced interleukin-10 secretion by in vitro stimulated monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation plays a role in maintaining the inflammatory process in Crohn's disease in some families. Patients and methods. We evaluated interleukin-10 Gly 15Arg in 379 patients with Crohn's disease, and 75 unrelated healthy controls. Also, first degree family members of interleukin-10 Gly 15Arg carriers were evaluated. Additionally, mutation carriers and their relatives were evaluated for CARD 15 R702W, G908R, and 1007fs. Results. Two patients with Crohn's disease were heterozygous for the interleukin-10 Gly 15Arg mutation. No homozygotes were found. The Glyl5Arg mutation was not observed in the controls. In first degree family members of the Crohn's disease-affected interleukin-10 Gly 15Arg carriers, the mutation was found in Crohn's disease-affected as well as in their apparently healthy individuals. All family members carried one or two CARD 15 mutation(s). Conclusion. The interleukin-10 Gly 15Arg mutation is rare in patients with Crohn's disease, and is not associated with the disease in the Netherlands. (c) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.