IL-2 PRODUCTION BY INTESTINAL LAMINA PROPRIA CELLS IN NORMAL INFLAMEDAND CANCER-BEARING COLONS

Biologically significant levels of IL-2 activity were produced by isol ated lamina propria mononuclear cells (LPMC) from normal intestine (n = 12), cancer-bearing colons (n = 35) and inflammatory bowel disease ( IBD) affected tissue (n = 12). The levels of IL-2 produced were simila r for all three sources of LPMC (normal 252 +/- 48 U/ml, IBD-affected mucosa 197 +/- 42 U/ml and colon cancer 285 +/- 43 U/ml). These levels were significantly greater than those produced by peripheral blood mo nonuclear cells (20 +/- 5 U/ml, P < 0.01) on a per cell basis. In muco sa from cancer-bearing colons the amount of IL-2 produced by LPMC was unaffected by the invasiveness of the colon cancer. LPMC IL-2 producti on was markedly suppressed by drugs used in IBD therapy. 5-Aminosalicy clic acid (5-ASA) reduced activity in a dose-dependent fashion. At a d ose equivalent to the faecal therapeutic level of 0.5 mg/ml activity, IL-2 production by LPMC was suppressed to 3.4% of controls. Similarly, exposure of LPMC to cyclosporin A (CyA) and hydrocortisone (HC) at th erapeutic levels reduced IL-2 activity to less than 1% of controls. Th e major producers of IL-2 activity were shown to be CD3+ T lymphocytes and those bearing the activation markers IL-2R and TFR. Suppression o f mucosal IL-2 production represents an important therapeutic mechanis m of drugs used in the management of IBD including HC, 5-ASA and CyA. These results suggest that mucosal T cells produce appreciable levels of IL-2 activity that may be important in maintaining immune homeostas is in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucos al lesions of IBD.