No inhibition of interferon gamma release in human lymphocytes by Ciamexone.
In previous experiments Ciamexone, derivative of 2-cyan-aziridine, was able to influence T-cell-mediated regulatory mechanisms but seemed to have no or only little effect on T cell effector mechanisms. On the basis of these observations Ciamexone seems to be a highly selective immunosuppressive agent. In order to evaluate further possible mechanisms of Ciamexone it was the aim of our investigation to study its influence on interferon gamma (IFN gamma) production in phytohaemogglutinin (PHA)-stimulated T lymphocytes of 15 tumour patients and 12 healthy reference subjects. The IFN gamma concentration of the cell supernatant was measured using an enzyme-linked immunosorbent assay. When the cells were stimulated with PHA at 7.5 micrograms/ml the IFN gamma concentration rose to significantly different values in the reference group (1.0 ng/ml) as compared to the tumour patients (0.4 ng/ml) (P less than 0.05). An addition of Ciamexone (at any of the concentrations administered) to PHA stimulation of peripheral blood mononuclear cells (PBMC) showed no influence on the IFN gamma release in either test group. The influence of hydrocortisone on the stimulation of PBMC with PHA resulted in a dose-dependent suppression of IFN gamma production in both test groups, again with significant differences between them. The IFN gamma concentration was 0.95 ng/ml in the reference group and 0.2 ng/ml in the tumour patients when 0.01 micrograms/ml hydrocortisone was added (P less than 0.05). At 10 micrograms/ml hydrocortisone suppressed IFN gamma production completely in both groups. Our results corroborate those investigations that showed no influence of the compound on T cell effector mechanisms. The attenuation of humoral immunophenomena, however, suggest a very specific point of action within the immune system by Ciamexone.
Baier
J
J
Medizinische Klinik der Ruhr-Universität Bochum, St. Josef Hospital, Federal Republic of Germany.
Neumann
H A
HA
Ricken
O
O
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001388:Aziridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D001388:Aziridines; D010835:Phytohemagglutinins; C035520:ciamexon; D007371:Interferon-gamma; D006854:Hydrocortisone