Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease

Background & Aims: Interleukin 10 (IL-10) is an anti-inflammatory, immunomodulatory cytokine that regulates mucosal inflammation. This study evaluated the safety, tolerance, and efficacy of recombinant human IL-10 (rhuIL-10) for mild to moderately active Crohn's disease. Methods: We conducted a 24-week multicenter, prospective, randomized, double-blind, placebo-controlled, and sequential-escalating-dose study. Ninety-five patients with Crohn's Disease Activity Index of 200-350, not presently undergoing corticosteroid, mesalamine, or immunosuppressive therapy, were treated with subcutaneous rhuIL-10 (1, 5, 10, or 20 μg/kg) or placebo once daily for 28 consecutive days. Patients were followed up for 20 weeks after treatment. Evaluation of safety and tolerance was the first objective, and efficacy was the second objective. Results: Adverse effects were dose-related, mild-to-moderate in severity, and reversible. Asymptomatic and reversible anemia and thrombocytopenia were observed at higher doses. No withdrawal or delayed adverse effects were evident during 20 weeks of follow-up. At the end of treatment (day 29), intent-to-treat analysis showed that 23.5% (confidence interval [CI], 6.8%-49.9%) of patients receiving 5 μg/kg rhuIL-10 experienced clinical remission and endoscopic improvement; 0% (CI, 0%-14.8%) of patients in the placebo group did. Higher doses of recombinant human IL-10 were less effective than 5 μg/kg. No rhuIL-10 serum accumulation and no antibody against IL-10 were detected after 4 weeks. Conclusions: Subcutaneous rhuIL-10 administered daily for 28 days to patients with mild to moderately active Crohn's disease is safe, well-tolerated, and shows clinical and endoscopic improvement.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Lack of evidence in vivo for nitrergic inhibition by Escherichia coli (STa) enterotoxin of fluid absorption from rat proximal jejunum

Fluid absorption from the proximal jejunum of the anaesthetised rat was measured in vivo by fluid recovery. As expected, heat stable (STa) enterotoxin from E. coli reduced fluid absorption. Neither intraperitoneal L-NAME, thought to inhibit a putative neurally mediated action of STa, nor similar doses of D-NAME, ameliorated the inhibitory effect on jejunal fluid absorption of STa. Luminally perfused 10 mM sodium nitroprusside (SNP) had no effect on fluid absorption when expressed per gram dry weight per hour but reduced fluid absorption when expressed per cm length per hour. Similarly, 80 but not 40 mg/Kg of L-NAME reduced fluid absorption when expressed per cm length per hour, while the same dose of D-NAME did not. L-NAME and SNP significantly increased the wet weight to dry weight and the length to dry weight ratio of perfused loops. We conjecture that smooth muscle relaxation caused by these compounds increases interstitial fluid volumes that can be misconstrued as changes in absorption when this is expressed per cm length or per tissue wet weight. When fluid absorption is expressed per gram dry weight of tissue, there is no evidence for a role of nitric oxide in normal or STa inhibited fluid absorption