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Mechanism of Action of Cyclosporin A
Author(s) -
BENDTZEN K.,
DINARELLO C. A.
Publication year - 1984
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1984.tb00976.x
Subject(s) - monokine , lymphokine , pinocytosis , receptor , mechanism of action , incubation , biology , chemistry , t cell , biochemistry , cytokine , interleukin , immune system , immunology , in vitro , endocytosis
Previous studies have shown that cyclosporin A (CyA) prevents the elaboration of the lymphokine leucocyte migration inhibitory factor (LIF). Since LIF production is interleukin 1 (IL‐1)‐dependent, we carried out experiments using partially and highly purified IL‐1 preparations to study the effect of CyA. We found that (a) IL‐1 was consistently depleted during a 1‐h incubation with human blood T lymphocytes but not with B lymphocytes or erythrocytes; (b) the depletion could not be ascribed to pinocytosis, cell functions requiring active metabolism, or enzyme‐mediated destruction of IL‐1; (c) CyA, but not biologically inactive cyelosporin, antagonized the apparent absorption of IL‐1; (d) T cells pre‐exposed to CyA were rendered incapable of removing the monokine; and (e) CyA was capable of displacing IL‐1 once absorbed by T cells. Because the putative binding of IL‐1 showed salurability. reversibility (with CyA as a probe), and tissue specificity consistent with a known target for the monokine, we propose that IL‐1 interacts with a receptor‐like structure on T cells. Finally, we found that insulin interfered with the function of CyA at the very early macrophage‐T‐cell co‐operative stage, even at physiological concentrations.