Linked Life Data

2942329

Source:http://linkedlifedata.com/resource/pubmed/id/2942329

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1986-9-17
pubmed:abstractText
In vitro effects of three immunosuppressive drugs, cyclosporin, methylprednisolone, and 6-mercaptopurine (the active moiety of azathioprine), have been assessed by various proliferative assays including mixed lymphocyte reaction (MLR), concanavalin A (Con A), OKT3 monoclonal antibody (MoAb), phorbol myristate acetate (PMA), and A23187 ionophore-induced mitogenesis. The influence of these drugs on the capacity to produce interleukin-2 (IL-2) after phytohemagglutinin (PHA) induction has also been evaluated. Depending upon the nature of the stimulus used, differences were found among the three immunosuppressive drugs, suggesting that different T-cell activation mechanisms are involved. The response to alloantigens (MLR) or to mitogens (Con A and OKT3 MoAb) resulted in significant inhibition by all three immunosuppressive agents, although 6-mercaptopurine was somewhat less potent at the pharmacological concentration of 0.1 microgram/ml. When PMA (which activates cells through protein kinase C) and A23187 ionophore (which enhances Ca2+ influx into the cytoplasm through membrane channels) were used, dissociations were observed, suggesting that drugs act differentially on early stages of T-cell activation. Inhibition of PMA-induced activation by cyclosporin was very limited in contrast to the potent effect of methylprednisolone. The latter drug could thus preferentially affect an activation step involving the PMA receptor. Furthermore, the inhibitory influence of methylprednisolone on A23187 ionophore-induced proliferation was equivalent to that of cyclosporin, while 6-mercaptopurine had no effect except at the high concentration of 1 microgram/ml in which direct inhibition of DNA replication is probably involved. IL-2 production induced by PHA was strongly blocked by methylprednisolone and cyclosporin but not by 6-mercaptopurine, at least when a pharmacological concentration was used. In view of the relative independence of ionophore-induced activation from the influence of IL-2, this response could be linked to the intrinsic mechanism of antiproliferative activity of immunosuppressive drugs which probably act mostly at the level of IL-2 production. These results also provide a cellular approach to the synergies between immunosuppressive drugs. Most of the tests are more strongly affected by cyclosporin than by 6-mercaptopurine, probably explaining the potent steroid-sparing effect of cyclosporin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0090-1229
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
422-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Differential in vitro actions of cyclosporin, methylprednisolone, and 6-mercaptopurine: implications for drugs' influence on lymphocyte activation mechanisms.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't