Circulating soluble factor-inhibiting natural killer (NK) activity of fresh peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease(IBD) patients

This study was performed in order to assess the cytotoxic activity, both na tural (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it with their clinical features. Cytotoxicity assays were perform ed using sensitive target cells for NK and ADCC activities. In some experim ents, highly purified NK cells, obtained both by Percoll density gradient a nd by co-culturing non-adherent PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we evaluated NK cell parameters such as nu mber, surface expression of adhesion molecules (CD11a/ CD18, CD49d and CD54 ) and response to different stimuli. We observed a decreased NK cytotoxicit y of PBMC from IBD patients, both in ulcerative colitis (UC) and Crohn's di sease (CD), independently of the clinical activity of disease. In contrast, the ADCC lytic activity was within normal range. The lower NK cytotoxic ac tivity observed in our IBD patients cannot be related to a decreased number of NK cells, surface expression of adhesion molecules, defective response to IL-2 and maturative defect. Decreased NK activity was induced in PBMC of controls when serum of patients was added and this was unrelated to monocy te-derived modulating factor(s). Our data show a decreased natural killing by fresh PBMC from IBD patients. This lower activity seems to be unrelated to a primary NK cell defect, since purified NK cells exhibited normal level s of killing. It might be hypothesized that serum factors, possibly derived from lymphocytes, with inhibitory properties on NK activity, might be func tionally active in the blood of IBD patients, thus modulating NK activity.