BACKGROUND: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of intestinal inflammation in inflammatory bowel disease. AIM: To investigate the in vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with Crohn's disease and patients with ulcerative colitis. METHODS: PBMCs and mucosal biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 determined by enzyme linked immunosorbent assays (ELISAs). RESULTS: PTX inhibited the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in cultures from controls, patients with Crohn's disease, and those with ulcerative colitis. The concentrations of IL-6 and IL-8 were not significantly modified 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.
BACKGROUND: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of intestinal inflammation in inflammatory bowel disease. AIM: To investigate the in vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with Crohn's disease and patients with ulcerative colitis. METHODS: PBMCs and mucosal biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 determined by enzyme linked immunosorbent assays (ELISAs). RESULTS:PTX inhibited the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in cultures from controls, patients with Crohn's disease, and those with ulcerative colitis. The concentrations of IL-6 and IL-8 were not significantly modified 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.
Authors: H C Reinecker; M Steffen; T Witthoeft; I Pflueger; S Schreiber; R P MacDermott; A Raedler Journal: Clin Exp Immunol Date: 1993-10 Impact factor: 4.330
Authors: L Schandené; P Vandenbussche; A Crusiaux; M L Alègre; D Abramowicz; E Dupont; J Content; M Goldman Journal: Immunology Date: 1992-05 Impact factor: 7.397
Authors: A Thanhäuser; N Reiling; A Böhle; K M Toellner; M Duchrow; D Scheel; C Schlüter; M Ernst; H D Flad; A J Ulmer Journal: Immunology Date: 1993-09 Impact factor: 7.397
Authors: A M Williams; C V Whiting; K Bonhagen; J Reimann; S Bregenholt; M H Claesson; P W Bland Journal: Clin Exp Immunol Date: 1999-06 Impact factor: 4.330
Authors: A Di Sabatino; R Ciccocioppo; B Cinque; D Millimaggi; R Morera; L Ricevuti; M G Cifone; G R Corazza Journal: Gut Date: 2004-01 Impact factor: 23.059