Inhibitory effect of suramin on receptor binding and cytotoxic activity of tumor necrosis factor alpha.
The effect of suramin on the binding of human Tumor Necrosis Factor alpha (huTNF alpha) to specific cell-surface receptors as well as on its cytotoxic activity in vitro was investigated. Suramin inhibited both activities in a dose-dependent manner. Experiments designed to discriminate if suramin exerted its inhibitory activity on the ligand or on the receptor showed that the ligand (huTNF alpha) was the most likely target for suramin in this system. These results may explain, in part, the immunosuppressive activities of suramin that have been observed in vivo and suggest that suramin could be useful in those disease states in which hyperproduction of huTNF alpha has been shown to play a pathogenic role.
Grazioli
L
L
Department of Immunology, Farmitalia Carlo Erba, Nerviano, Italy.
Alzani
R
R
Ciomei
M
M
Mariani
M
M
Restivo
A
A
Cozzi
E
E
Marcucci
F
F
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013498:Suramin