Suppression of Immune and Hemopoietic Cellular Responses by Methisazone

Abstract

The antiviral drug methisazone (N-methylisatin ,B-thiosemicarbazone) was tested for its effect on immune responses to sheep erythrocytes and on hemopoietic colony-forming cell (granulocyte-macrophage progenitor cell) responses to complete Freund's adjuvant in mice. Suppressive activity was demonstrated in both systems, the immune system being more readily and more consistently susceptible. Evidence is presented which suggests that the insoluble particulate form of the drug has both stimulatory and suppressive effects on the colony-forming cell system, whereas the soluble form is only suppressive. Methisazone increased the mortality from ectromelia in adjuvant-treated animals.

Inhibition of Granulocyte-Macrophage Colony Formation In Vitro by Substituted Isatin Thiosemicarbazones

“…The present observations confirm for methisazone and extend to other related and more active compounds the finding of an inhibitory effect restricted to the early phase of the differentiation pathway. The implications in terms of antileukemia or immunosuppressive therapy have been previously referred to (6,7). The present observations on mouse marrow extend the range of possible agents available for such investigations, and the preliminary work with human VOL.…”

The Thiosemicarbazones

“…8). McNEILL et al (1972) found that the number of IgM-producing lymphocytes was reduced almost 5-fold compared with the number found in drug-free mice. There was almost a 20-fold difference when the number of IgG-producing cells was determined.…”

“…The initial quantitative studies on the ability of thiosemicarbazones to inhibit the immune response in mice were carried out by McNEILL (1972McNEILL ( , 1973 and McNEILL et al (1972). The humoral response to sheep red blood cells (see Sect.…”

“…In line with these observations, the amount of circulating antibody against SRBCs 5 days after beginning the drug treatment was 15-fold lower than in the control group of mice. Since antibody-secreting cells are derived from the bone marrow, McNEILL et al (1972) next determined that the total number of cells which could be flushed from femurs was the same whether or not mice had received six daily injections ofMIBT. They also established the number of cells in these preparations capable of forming colonies in a semisolid suspension cell assay.…”

“…G.II), it was established that MIBT inhibited both the B-cell and T-cell response (BORYSIEWICZ et al 1977;ZGORNIAK-NowOSIELSKA et al 1978). The B-cell, or humoral response, was measured in the same way as reported by McNEILL et al (1972) except that mice received 20 mg kg-1 day-l MIBT after a single injection of SRBCs. The T-cell, or cell-mediated response was measured by the degree of allergic contact dermatitis provoked by oxazolone, using the same regimen of drug administration as previously described.…”