IL-10-producing regulatory B cells induced by IL-33 (BregIL-33) effectively attenuate mucosal inflammatory responses in the gut

Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10-/-) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19+CD25+CD1dhiIgMhiCD5-CD23-Tim-1-) of IL-10 producing Breg-like cells (BregIL-33) was identified responsible for the protection. We demonstrated further that BregIL-33 isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10-/- mice. Our findings indicate an essential protective role, hence therapeutic potential, of BregIL-33 against mucosal inflammatory disorders in thegut. © 2014.link_to_subscribed_fulltex

Budesonide foam vs. hydrocortisone acetate foam in the treatment of active ulcerative proctosigmoiditis

INTRODUCI'ION: Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema. Foam offers patients better tolerability than an enema. In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam. METHODS: Two hundred fifty-one patients with proctosigmoiditis were randomly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks. RESULTS: Remission rates were comparable in the budesonide and hydrocortisone groups, 53 and 52 percent, respectively. The mean disease activity index for the two groups decreased to a similar extent, from 7.2 +/- 1.9 and 7 +/- 2 to 3.6 +/- 3.1 and 3.9 +/- 3.4 in the budesonide and hydrocortisone groups, respectively. In a subgroup of patients who had not responded to rectal administration of mesalamine, 23 of 44 (52 percent) patients who received budesonide responded favorably to the foam, as compared with 14 of 38 (37 percent) patients who received hydrocortisone (P = not significant). Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients. CONCLUSIONS: This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis

Interleukin-33 exacerbates acute colitis via interleukin-4 in mice

Interleukin-33 (IL-33) and its receptor ST2 are over-expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL33 and ST2 are the primary early genes induced in the inflamed colon of BALB/c mice following dextran sulphate sodium (DSS)-induced experimental ulcerative colitis. Accordingly diarrhoea and DSS-induced colon inflammation were impaired in ST2−/− BALB/c mice and exacerbated in wild-type mice by treatment with exogenous recombinant IL-33, associated respectively with reduced and enhanced expression of chemokines (CXCL9 and CXCL10), and inflammatory (IL-4, IL-13, IL-1, IL-6, IL-17) and angiogenic (vascular endothelial growth factor) cytokines in vivo. The exacerbation effect of treatment with recombinant IL-33 on DSS-induced acute colitis was abolished in IL-4−/− BALB/c mice. Hence, IL-33 signalling via ST2, by inducing an IL-4-dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis