Enhand secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina ropria monouclear cells from patients with ulcretive cilitis and Crohn's disease

Abstract

SUMMARY: The perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulalion of cylokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-α), IL-6 and IL-1β, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isoiated from involved inflammatory bowel disease (lBD) mucosa spontaneously produced increased amounts of TNF-α, IL-6, and IL-1β. The TNF-α secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-α and IL-1β by LPMNC from patients with either uicerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from noninvolved ulcerative colitis mucosa secreted markedly increased leveis of IL-6 compared with noninvolved Crohn's disease mucosa or control mucosa. The heightened lL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologie mechanisms involved in the initiation of inflammation may differ between ulceralive colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoseopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.