IL-10 SYNERGIZES WITH IL-4 AND IL-13 IN INHIBITING LYSOSOMAL-ENZYME SECRETION BY HUMAN MONOCYTES AND LAMINA PROPRIA MONONUCLEAR-CELLS FROM PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated with enhanced monocytic lysosomal enzyme release. In this study, peripheral monocytes and lamina propria mononuclear cells (LPMN C) were isolated from IBD patients and normal controls. Cells were sti mulated with lipopolysaccharide after treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using the corresponding p- nitrophenyl glycosides as substrates. Molecular forms of cathepsin D w ere examined to describe the mode of enzyme release. IL-10 and IL-4-st rongly down-regulate enzyme secretion in IBD monocytes, IBD monocytes showed a diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte response was not found with combinations of IL-13 an d IL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed signi ficantly higher enzyme secretion compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL-4 or IL-10 and I L-13 strongly suppressed enzyme release by these cells. Both the precu rsor and mature forms of cathepsin D were elevated in IBD patients. Wh ile IL-13 reduced mainly the precursor form, the effect of IL-4 and IL -10 concerns both the precursor and mature form of cathepsin D, Our re sults favor the potent clinical utility of combined treatment, thus im proving chances of developing effective treatments for human IBD.