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Effect of Rifamycin-SV Derivatives on Immunologic Responses in Culture¹

From the Department of Medicine, University of Toronto and the Ontario Cancer Institute, Toronto, Ontario, Canada M4X 1K9

Abstract

Both rifampicin and 4-N-demethyl rifampicin (AF/AP) inhibited the formation of plaque-forming cells to sheep erythrocytes at concentrations that did not affect the formation of myeloid colonies in culture. Two other rifamycin-SV derivatives, 4-N-benzyl demethyl rifampicin (AF/ABP) and 2,6-dimethyl-4-benzyl-4-demethyl rifampicin (AF/ABDP CIS) had no significant effect on either the formation of plaque-forming cells or myeloid colonies. Rifampicin and AF/AP also inhibited the incorporation of tritiated thymidine in one-way mixed leukocyte reactions both by mouse spleen cells and by human peripheral blood leukocytes, and AF/AP markedly inhibited the generation of cytotoxic effector cells in the mixed leukocyte reaction by mouse spleen cells. The action of AF/AP on the formation of plaque-forming cells appears to affect an earlier cellular function than does rifampicin. Although the precise nature of the pharmacologic effect of these drugs on the formation of antibody-forming cells and on the generation of cytotoxic effector cells is unknown, the inhibitory effect of at least some of the members of this family of drugs on viral RNA-dependent DNA polymerase (reverse transcriptase) suggests that reverse transcriptases may be involved in antibody formation by normal cells of the immunologic system.

Footnotes

¹ This work was supported by the Medical Research Council of Canada (MA-1609).

² Associate of the Medical Research Council of Canada.