Acknowledgements We are indebted co many past and present members of our lab and to our external collaborators for their contributions in the shaping of ideas presented in this review. We would like to extend many thanks to Jonathon Sedgewick for critical discussions on the EAE concepts and Anastasia Kotanidou, Hospital Evangelismos, for providing patient blood samples, This work was supported in part by the Hellenic Secretariat for Research and Technology and European Commission Grants BIO4-CT96-0077 and BIO4-CT-96-0174.
On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease
Article first published online: 28 APR 2006
Volume 169, Issue 1, pages 175–194, June 1999
How to Cite
Kollias, G., Douni, E., Kassiotis, G. and Kontoyiannis, D. (1999), On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Immunological Reviews, 169: 175–194. doi: 10.1111/j.1600-065X.1999.tb01315.x
- Issue published online: 28 APR 2006
- Article first published online: 28 APR 2006
Summary: The specific role of the tumor necrosis factor (TNF)/TNF receptor (TNFR) system in disease pathogenesis still remains an unresolved puzzle. Recent studies in transgenic and knockout animals, where the pathogenic influence of genetically perturbed TNF expression has been evaluated, indicate that several pathways of TNF/TNFR action may contribute independently or in concert to initiate, promote or downregulate disease pathogenesis. Evidently, organ-specific inflammatory or autoimmune pathology may ensue due co sustained activation by TNF of innate immune cells and inflammatory responses, which may consequently lead to tissue damage and co organ-specific chronic pathology. However, more cryptic functions of this molecule may be considered Co play a significant pare in che development of TNF-mediated pathologies. Direct interference of TNF with the differentiation, proliferation or death of specific pathogenic cell targets may be an alternative mechanism for disease initiation or progression. In addition Co these activities, there is now considerable evidence to suggest that TNF may also directly promote or downregulate the adaptive immune response. It is therefore evident that no general scenario may adequately describe the role of TNF in disease pathogenesis. In this article, we aim to place these diverse functions of TNF/TNFRs into context with the development of specific pathology in murine models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.