RT Journal Article
SR Electronic
T1 A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 6276
OP 6282
VO 159
IS 12
A1 Plevy, S E
A1 Landers, C J
A1 Prehn, J
A1 Carramanzana, N M
A1 Deem, R L
A1 Shealy, D
A1 Targan, S R
YR 1997
UL http://www.jimmunol.org/content/159/12/6276.abstract
AB Recent clinical studies of Crohn's disease patients demonstrated dramatic clinical responses following one i.v. infusion of a chimeric mAb to TNF-alpha (cA2). To assess the role of TNF-alpha in mucosal cytokine regulation, the effects of TNF-alpha on lamina propria mononuclear cell (LPMC) Th1 production were determined. Increased IFN-gamma production was demonstrated in anti-CD2-stimulated LPMC cultured in TNF-alpha. To determine the effects of cA2 on cytokine production, TNF-alpha- and IFN-gamma-producing cells were quantitated in LPMC from five Crohn's disease patients treated with cA2. In all four patients who demonstrated clinical and endoscopic improvement, decreased numbers of LPMC producing IFN-gamma and TNF-alpha following CD2/CD28 activation paralleled improvement in disease activity over 8 wk. In one patient who did not improve, increased numbers of TNF-alpha- and IFN-gamma-secreting LPMC were observed. In three of four responding patients, CD2/CD28-activated PBMC demonstrated increased IFN-gamma production over 8 wk. These observations suggest that TNF-alpha may be a cofactor for mucosal Th1 responses, and improvement in clinical parameters and intestinal inflammation induced by cA2 in Crohn's disease may be mediated by down-regulation of mucosal Th1 cytokines.