Anti Inflammatory Cytokines

IL-10, discovered in 1989, has shown potent antiinflammatory properties in in vitro and in vivo animal studies. IL-10 exerts its anti-inflammatory effects by down-regulating production of proinflammatory cytokines by dendritic cells, macrophages and mono-cytes. In clinical trials, a modest benefit was observed in patients treated with subcutaneous injection of humanised IL-10 [158-161]. In postsurgical CD

patients, IL-10 administration did not show any effect [162]. The efficacy of IL-10 is lower than expected, probably as a consequence of the stimulation of INF-y production [158]. Furthermore, serum levels and tissue concentrations of IL-10 are generally elevated in CD patients [5].

Recent experimental studies demonstrated that the delivery of tissutal immunoregulatory proteins, including IL-10, by gene therapy may be a potentially exciting approach to treatment of IBD [163]. Future challenges for using gene therapy in CD will be to establish safety, localisation and duration of the expression of the transduced gene, as well as to ensure that delivery of immunoregulatory proteins is therapeutic.

IL-11 has been shown to be expressed and have activity in multiple other tissues, including gut, but to date, the physiologic role of this protein remains unknown. Preliminary data on short-term treatment with humanised IL-11 demonstrated that given sub-cutaneously for 3 weeks (16 mg/kg per week), the drug is well tolerated in patients with active CD [164]. A recent randomised trial reported that weekly subcutaneous injection with rhIL-11 (15 mmg/kg per week) compared with placebo is effective in inducing remission in patients with active CD [165]. Potentially, IL-11 may be an alternative or sparing agent for corticosteroids in the management of CD, but its role remains unclear.

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