Effect of Vinblastine on the Early Events in the Humoral Immune Response of Mice to SRBC

Abstract

The effect of vinblastine (VLB), a mitotic blocking agent, on the number of plaque-forming cells (PFC) and on the metabolic activities of spleen cells of mice reimmunized with SRBC was studied. When VLB (75 μg/mouse) and antigen were administered simultaneously, the number of PFC, on the 4th day after immunization, was reduced to 40% of control levels. However, when the same amount of VLB was administered to mice 24 h after immunization, it reduced the number of PFC to 10% of control levels. The possibility that VLB exerts a specific cytotoxic effect on preformed PFC either in vivo or in vintro was ruled out. A direct profound effect of VLB on antigen-stimulated cells was observed when VLB was injected 24 h after reimmunization, and the incorporation rates of radioactive precursors into macromolecules by spleen cells were measured at 4-hour intervals. VLB suppressed completely the antigen-induced peak of 3H-thymidine incorporation, while it had no effect on the incorporation rate of ³H-uridine and only a slight effect on the incorporation rate of ³H-amino-acids by the same cells. The results suggest that the decrease in number of PFC caused by injection of VLB 24 h after immunization is due to prevention by VLB, of precursor cells from going through a critical cell division, which takes place later than 24 h after immunization. Thus, at least one cell division is required for an immune response in vivo.

Classification of Chemotherapeutic Agents Based on Their DifferentialIn vitroEffects on Dendritic Cells

“…Our findings may first appear contradictory to the general notion of VBL as a chemotherapeutic drug with immunosuppressive potentials. Indeed, VBL has been reported to inhibit mitogen-induced lymphocyte activation (24), induction of cytotoxic T cell activity (25), tumorcidal potential of macrophages (26), natural killer cell-mediated cytotoxicity (27), antibody-dependent cell-mediated cytotoxicity (28), humoral immune responses (29), cellular immune protection against microbial infection (30), and host anti-tumor immunity (31). However, most of those immunosuppressive properties were observed for VBL at relatively high concentrations and/or after repeated administrations.…”