Interleukin 2 activity of human intestinal mucosa mononuclear cells. Decreased levels in inflammatory bowel disease

Abstract

Interleukin 2, a soluble product of activated T lymphocytes, is of central importance in the development of an appropriate T-cell immune response. Defects in the production of or response to this lymphokine have been described in a variety of immune deficiency and autoimmune states, thus suggesting a role in the pathogenesis of such disorders. To investigate potential abnormalities of interleukin 2 in inflammatory bowel disease, we measured its activity in cultures of intestinal mucosa mononuclear cells derived from Crohn's disease and ulcerative colitis patients. Lamina propria mononuclear cells from inflamed and control tissues were incubated with phorbol myristate acetate, and the amount of the lymphokine in the supernatants was quantitated in a biological assay using cloned, interleukin 2-dependent, cytotoxic mouse T-cell lines. We found that, in culture supernatants of cells from both forms of inflammatory bowel disease, interleukin 2 levels were significantly lower than those detected in cultures containing cells from histologically normal mucosa. Low levels were not correlated to duration, clinical activity, and anatomical location of the disease process or corticosteriod therapy. Deficient activity of this essential growth factor could contribute to abnormal T-cell proliferation and clonal expansion at the gut mucosal level, perhaps inducing a defective immune response leading to a chronic inflammatory reaction in Crohn's disease and ulcerative colitis.