Differences in the intrinsic capacity of peripheral blood mononuclear cells to produce tumor necrosis factor alpha and 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), with ulcerative colitis (UC), and 23 healthy controls (HC) were cultured for 48 h in the presence 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) 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 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.
Bouma
G
G
Dept. of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands.
Oudkerk Pool
M
M
Scharenberg
J G
JG
Kolkman
J J
JJ
von Blomberg
B M
BM
Scheper
R J
RJ
Meuwissen
S G
SG
Peña
A S
AS
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha