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A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn’s disease
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.
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Citations
Cited by
Molecular Mechanisms RegulatinG Th1 Immune Responses
Szabo, S. J., Sullivan, B. M., Peng, S. L., & Glimcher, L. H. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.140942 · Cited by 1,019
The genetics and immunopathogenesis of inflammatory bowel disease
Cho, J. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2340 · Cited by 940
Anti–Interleukin-12 Antibody for Active Crohn's Disease
Mannon, P. J., Fuss, I. J., Mayer, L., Elson, C. O., Sandborn, W. J., Present, D., Dolin, B., Goodman, N., Groden, C., Hornung, R. L., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033402 · Cited by 848
Tiede, I., Fritz, G., Strand, S., Poppe, D., Dvorsky, R., Strand, D., Lehr, H. A., Wirtz, S., Becker, C., Atreya, R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16432 · Cited by 828
Neurath, M. F., Weigmann, B., Finotto, S., Glickman, J., Nieuwenhuis, E., Iijima, H., Mizoguchi, A., Mizoguchi, E., Mudter, J., Galle, P. R., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011956 · Cited by 607
Metadata
- Authors
- Plevy, S. E., Landers, C. J., Prehn, J., Carramanzana, N. M., Deem, R. L., Shealy, D., & Targan, S. R.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-12
- Volume
- 159
- Issue
- 12
- Pages
- 6276-6282
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1901931884
- Cited by
- 385
- References
- 0
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn’s disease. https://app.cochat.ai/papers/10.4049/jimmunol.159.12.6276
- The paper
- Plevy, S. E., Landers, C. J., Prehn, J., Carramanzana, N. M., Deem, R. L., Shealy, D., & Targan, S. R. (1997). A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn’s disease. The Journal of Immunology. https://doi.org/10.4049/jimmunol.159.12.6276
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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