A human tumor necrosis factor p75 receptor agonist stimulates in vitro T cell proliferation but does not produce inflammation or shock in the baboon.
Open Access
- 1 July 1996
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 184 (1), 165-171
- https://doi.org/10.1084/jem.184.1.165
Abstract
Tumor necrosis factor (TNF) is a potentially useful adjunct to anticancer therapies. However, the clinical utility of TNF has been limited by generalized toxicity and hypotension. Recently, studies have begun to dissect the individual proinflammatory and immunologic responses that result from TNF binding to its two cellular receptors, p55 and p75, in an attempt to develop TNF receptor agonists with reduced systemic toxicity. To evaluate a p75 receptor selective TNF mutant (p75TNF), TNF and p75TNF were administered to healthy anesthetized baboons. Intravenous infusion of the p75TNF produced none of the hemodynamic changes seen after the infusion of TNF. Infusion of p75TNF also failed to induce the plasma appearance of interleukins 6 and 8. However, p75TNF enhanced in vitro baboon thymocyte proliferation to concanavalin A, and infusion of p75TNF resulted in increased soluble p55 and p75 receptor plasma concentrations. Local skin necrosis and tissue neutrophil infiltration were seen after subcutaneous injections of TNF and p55TNF. Subcutaneous injection of p75TNF did not result in skin necrosis but did result in a modest dermal infiltration of lymphocytes and macrophages. The findings suggest that p75TNF may stimulate T cell proliferation without the systemic and local toxicity seen with TNF.Keywords
This publication has 25 references indexed in Scilit:
- Monoclonal antibodies specific for murine p55 and p75 tumor necrosis factor receptors: identification of a novel in vivo role for p75.The Journal of Experimental Medicine, 1995
- A human tumor necrosis factor (TNF) alpha mutant that binds exclusively to the p55 TNF receptor produces toxicity in the baboon.The Journal of Experimental Medicine, 1994
- Lymphotoxin Lacks Effects on 75-kDa Receptors in Cytotoxicity on U-937 CellsBiochemical and Biophysical Research Communications, 1994
- Tumor necrosis factor activities and cancer therapy — A perspectivePharmacology & Therapeutics, 1993
- Regional therapy of melanomaEuropean Journal Of Cancer, 1993
- Mice lacking the tumour necrosis factor receptor 1 are resistant to IMF-mediated toxicity but highly susceptible to infection by Listeria monocytogenesNature, 1993
- Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.The Journal of Experimental Medicine, 1993
- The Pathophysiology of Tumor Necrosis FactorsAnnual Review of Immunology, 1992
- Acute and chronic inflammatory responses to local administration of recombinant IL-1α, IL-β, TNFα, IL-2 and Ifnγ in miceInflammation Research, 1989
- Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo.The Journal of Experimental Medicine, 1989