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A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.

S E Plevy, C J Landers, J Prehn, N M Carramanzana, R L Deem, D Shealy and S R Targan
J Immunol December 15, 1997, 159 (12) 6276-6282;
S E Plevy
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C J Landers
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J Prehn
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N M Carramanzana
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R L Deem
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D Shealy
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S R Targan
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Abstract

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.

  • Copyright © 1997 by American Association of Immunologists
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The Journal of Immunology
Vol. 159, Issue 12
15 Dec 1997
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A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.
S E Plevy, C J Landers, J Prehn, N M Carramanzana, R L Deem, D Shealy, S R Targan
The Journal of Immunology December 15, 1997, 159 (12) 6276-6282;

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A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease.
S E Plevy, C J Landers, J Prehn, N M Carramanzana, R L Deem, D Shealy, S R Targan
The Journal of Immunology December 15, 1997, 159 (12) 6276-6282;
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Print ISSN 0022-1767        Online ISSN 1550-6606