Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-11-16
pubmed:abstractText
Earlier studies from our laboratory have demonstrated that phenothiazine derivatives are capable of inhibiting mitogen-induced activation of human T-cells and thymocytes. Similar to cyclosporin A, phenothiazine derivatives exert these inhibitory effects by decreasing the accumulation of lymphokine-specific mRNA. However, proliferation of T-cell blasts and of unfractionated human thymocytes can also be induced by interleukin 2. Since activation of T-cells via the interleukin 2 receptor seems to be resistant to the action of cyclosporin A, the present study was designed to investigate whether lymphokine-induced activation could be inhibited by phenothiazine derivatives. The effects of the phenothiazine derivatives chlorpromazine and/or fluphenazine have been studied and compared to the action of cyclosporin A and FK506 in human thymocytes, human T-cell blasts and in the human T-cell line H33-HJ JA1, which is an interleukin 2 producing cell line derived from Jurkat cells. As evidenced by the incorporation of [3H]-thymidine, cyclosporin A (1 microgram/ml) and FK506 (100 ng/ml) have no or only marginal inhibitory capacity on interleukin 2-induced proliferation in all T-cell systems tested. By contrast, phenothiazine derivatives (fluphenazine > chlorpromazine) exert a dose-dependent inhibition of the activation of these cells in pharmacologically relevant micromolar concentrations. Similar results were obtained by measuring the production of interferon-gamma in the supernatants of interleukin 2-induced human thymocytes. Our results suggest that the use of phenothiazines might be helpful in immunosuppressive regimens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
350
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
100-3
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Inhibition of cyclosporin A/FK506 resistant, lymphokine-induced T-cell activation by phenothiazine derivatives.
pubmed:affiliation
Medizinische Klinik III, Universitätsklinikum Grosshadern, München, Germany.
pubmed:publicationType
Journal Article