Time-dependence and selectivity of immunosuppressive agents.

The effects of a variety of agents on the mouse antibody response to sheep red cells (SRC) and Escherichia coli lipopolysaccharide (LPS) were investigated. Agents formed two broad groups according to the time-dependence of their effects. Class I agents inhibited responses if given at any time over a broad period from before administration of antigen to 1-2 days afterwards. They included ionizing radiation, cortisone acetate, cholera toxin and several alkylating agents. Class II agents inhibited responses substantially only if given 1-2 days after the antigen. These agents were all either antimetabolites or vinca alkaloids. Class II agents had only moderate selectivity. When given at the time of maximal effectiveness they usually suppressed the response to SRC more than that to LPS. Some class I agents had striking selectivity. Radiation, cortisone acetate, and cholera toxin markedly suppressed the SRC response but had much less effect on the LPS response. In contrast, mitoclomine and its analogues, which are lipid-soluble alkylating agents, suppressed the response to LPS far more than that to SRC. Possible reasons for these differences in time-dependence and selectivity are discussed.