IL-2 production by intestinal lamina propria cells in normal inflamed and cancer-bearing colons

Open Access
Publisher Website
Google Scholar
Abstract
Biologically significant levels of IL-2 activity were produced by isolated lamina propria mononuclcar 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 similar for all three sources of LPMC (normal 252 ± 48 U/ml, I BD-affected mucosa 197 ± 42 U/ml and colon cancer 285 ± 43 U/ml). These levels were significantly greater than those produced by peripheral blood mononuclcar cells (20·5 U/ml, P < 0·01) on a per cell basis. In mucosa from cancer-bearing colons the amount of IL-2 produced by LPMC was unaffected by the invasiveness of the colon cancer. LPMC IL-2 production was markedly suppressed by drugs used in IBD therapy. 5-Aminosalicylic acid (5-ASA) reduced activity in a dose-dependent fashion. At a dose 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 therapeutic levels reduced I L-2 activity to less than 1% of controls. The major producers of IL-2 activity were shown to be CD3+ T lymphocytes and those bearing the activation markers IL-2R and TFR. Suppression of mucosal IL-2 production represents an important therapeutic mechanism ofdrugs 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 homeostasis in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucosal lesions of IBD.