IN-VITRO EFFECTS OF OXPENTIFYLLINE ON INFLAMMATORY CYTOKINE RELEASE IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Background-Inflammatory cytokines, including tumour necrosis factor-al pha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as p rimary mediators of intestinal inflammation in inflammatory bowel dise ase. Aim-To investigate the in vitro effects of oxpentifylline (pentox ifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inf lamed intestinal mucosa cultures from patients with Crohn's disease an d patients with ulcerative colitis. Methods-PBMCs and mucosal biopsy s pecimens were cultured for 24 hours in the absence or presence of PTX (up to 100 mu g/ml), and the secretion of TNF-alpha, IL-1 beta IL-6, a nd IL-8 determined by enzyme linked immunosorbent assays (ELISAs). Res ults-PTX inhibited the release of TNF-alpha by PBMCs from patients wit h inflammatory bowel disease and the secretion of TNF-alpha and IL-1 b eta by organ cultures of inflamed mucosa from the same patients. Secre tion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concent ration of 25 mu g/ml (IC50). PTX was equally potent in cultures from c ontrols, patients with Crohn's disease, and those with ulcerative coli tis. The concentrations of IL-6 and IL-8 were not significantly modifi ed in PBMCs, but IL-6 increased slightly in organ culture supernatants . Conclusions-PTX or more potent related compounds may represent a new family of cytokine inhibitors, potentially interesting for treatment of inflammatory bowel disease.