The researchers investigated the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD).
They reported their findings in the February issue of Gut.
Thalidomide improves clinical symptoms in patients with therapy-refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect is, however, still unknown.
Ten patients with therapy-refractory IBD (9 Crohn's disease, 1 ulcerative colitis) were enrolled in the trial. Each received thalidomide 300 mg daily in a 12-week open label study.
Production of TNF-alpha, interleukin (IL)-1-beta, IL-6, and IL-12 was investigated in short-term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC). This was done both before and after 12 weeks of treatment.
In addition, LPMC were cultured with graded doses of thalidomide.
| Thalidomide decreased TNF-alpha and IL-12 levels, but had no effect on IL-1-beta and IL-6.
Three patients discontinued treatment because of sedative side-effects.
In the other patients, disease activity decreased significantly, with 4 patients achieving remission.
Production of TNF-alpha and IL-12 decreased during treatment with thalidomide: LPMC (TNF-alpha: 42.3 pg/ml before treatment vs 16.4 after treatment; IL-12: 9.7 vs 5.0) and PBMC (TNF-alpha: 62.8 vs 22.5).
It was found that production of IL-1-beta and IL-6 did not change significantly.
Culturing of LPMC with thalidomide showed a dose-dependent decrease in TNF-alpha and IL-12 production.
Dr Juergen Bauditz, of the Charité University Hospital in Berlin, concluded, "The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-alpha and IL-12."