Year: 1993
Type: article
Abstract: Despite the many achievements in allotransplantation, the major problems are still the lack of early and reliable markers as well as the shortage of effective immunosuppressive agents for graft rejection. Up to now, allograft rejection is usually diagnosed by relatively nonspecific markers of inflammation or on the basis of organ function tests. The definitive standard remains histological examination of tissue from the biopsy of graft. However, increased knowledge of the cytokines and the development of specific and accurate assays have recently led to the possibility of analyzing immune rejection using less invasive procedures. Cytokines, as major components of both specific cellular and humoral immune responses, are mediators of cellular communication. The research of cytokines has been a field of extraordinary development in organ transplantation during the last decade37). Recent studies have revealed that Tumor Necrosis Factors (TNFs), one kind of major cytokines, are not only limited to necrosing tumor cells, but play a very important role in the initiation and regulation of immunoreaction on allograftl,4,15,22). Bioimmunochemically, TNFa /cachectin and TNF/3 /lymphotoxin represent two closely linked cytokines with cytostatic and cytotoxic activity in mediating the pathogenesis of acute rejection during the course of post-transplantation. TNFs mediate beneficial or deleterious biological effects depending on the quantity produced, the duration of release, and biochemical milieu of the responding cells39). TNFa is mainly synthesized from activated monocytes or macrophages while TNF/3 is produced from stimulated T-lymphocytes and some transformed B-lymphoblastoid cells. These molecules share 36% identity and 51% homology in their overall aminoacid sequences. They also share common receptor binding domains as well as exert similar immunologic effects. The major difference in these two compounds is that TNF/3 is a glycoprotein while TNFa contains no carbohydrate. Gene structure analysis demonstrates that both these molecules were derived from a similar ancestral gene and they may be highly cons.erved across species 7•11•21·39). A large number of papers reported that elevated TNFs level could be found in serum, urine and graft tissue before or during rejection episodes in recipients following organ allotransplantation. On the other hand, a significant effect following anti-TNFs therapy alone or a synergistic response in combination with immunosuppressive agents have been successfully applied as new approaches to immunosuppression for allotransplantation. In this article, the authors will review the beneficial effectiveness of predicting rejection by measuring TNFs level and the therapeutic potential of antiTNFs treatment in allotransplantation.
Source: PubMed
Authors: Z G Zhu, T Asahara, H Yahata, E Ono, S Marubayashi, H Watanabe, Y Fukuda, K Dohi
Institution: Hiroshima University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1870832754