DIFFERENCES IN THE INTRINSIC CAPACITY OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS TO PRODUCE TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA IN PATIENTS WITH INFLAMMATORY-BOWEL-DISEASE AND HEALTHY CONTROLS

Background: Tumor necrosis factor alpha (TNF alpha) and beta (TNF beta) appear to play an important role in the regulation of the inflammatory response. The aim of the present study was to investigate the intrinsic capacity of peripheral blood mononuclear cells (PBMC) to produce these cytokines. Methods: PBMC from 41 patients with Crohn's disease (CD), 32 with ulcerative colitis (UC), and 23 healthy controls (HC) were cultured for 48h in the presence or absence of the T-cell activators anti-CD3 and anti-CD28. Biologically active total TNF (TNF alpha and beta), TNF alpha, and TNF beta production were measured using a bioassay for biologically active TNF and specific TNF alpha and TNF beta enzyme-linked immunosorbent assays. Results: Large interindividual differences in TNF production were observed. Production of biologically active TNF after T-cell stimulation was significantly decreased in UC patients as compared with HC and CD patients (median, 337 U/ml, 800 U/ml, and 1050 U/ml, respectively). Stimulated TNF alpha production in UC patients (median, 432 U/ml) and in CD patients (median, 537 U/ml) did not differ statistically significantly from HC (median, 730 U/ml). In contrast, stimulated TNF beta production was significantly increased in CD patients (median, 1637 U/ml) as compared with HC and UC patients (median, 800 U/ml and 837 U/ml, respectively). Conclusions: These findings support the concept that UC and CD are not two homogeneous, clearly distinguishable disease entities but rather a heterogeneous group of diseases. Studies directed to assess the immunogenetic background of these different disease manifestations in IBD are underway.