In vitro effects of oxpentifylline on inflammatory cytokine release in patients with inflammatory bowel disease

Gut. 1997 Apr;40(4):475-80. doi: 10.1136/gut.40.4.475.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colitis, Ulcerative / immunology
  • Colon / immunology
  • Crohn Disease / immunology
  • Culture Techniques
  • Cytokines / metabolism*
  • Female
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / immunology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Pentoxifylline / pharmacology*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Pentoxifylline