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Kinetics of soluble TNF‐receptors and soluble adhesion molecules ICAM‐1, E‐selectin and VCAM‐1 under systemic rhTNFα therapy
Author(s) -
Boehme M. W. J.,
Waldherr R.,
Kist A.,
Riedl S.,
WalterKirst R.,
Kempeni J.,
Raeth U.
Publication year - 1996
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1996.151301.x
Subject(s) - tumor necrosis factor alpha , cell adhesion molecule , vcam 1 , cytokine , intercellular adhesion molecule 1 , in vivo , icam 1 , cell adhesion , receptor , immunology , e selectin , ex vivo , cancer research , endothelial stem cell , necrosis , in vitro , chemistry , biology , medicine , cell , pathology , biochemistry , microbiology and biotechnology
Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF‐α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti‐tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E‐selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF‐α (rhTNF‐α). All tests were performed by enzyme‐linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF‐α therapy was poor. Only one patient with isolated intra‐arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour‐specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF‐α therapy in addition to cytokine‐dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.