IL-2 production by intestinal lamina propria cells in normal inflamed and cancer-bearing colons.
Biologically significant levels of IL-2 activity were produced by isolated 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 similar 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 mononuclear cells (20 +/- 5 U/ml, P less than 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 IL-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 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 homeostasis in the normal intestine, provide anti-neoplastic cytotoxic activity and contribute to the inflammatory events that characterize the mucosal lesions of IBD.
Pullman
W E
WE
Imperial Cancer Research Fund, London, UK.
Doe
W F
WF
D000636:Aminosalicylic Acids / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D019804:Mesalamine
D000636:Aminosalicylic Acids; D007376:Interleukin-2; D019804:Mesalamine; D016572:Cyclosporine; D006854:Hydrocortisone