The effect of cytotoxic agents on the primary immune response to Listeria monocytogenes.

Tripathy, S.P.; Mackaness, G.B.

The Journal of Experimental Medicine; 1969; 130; 1-16.

Drugs used in the chemotherapy of cancer have also been used as immunosuppressive agents for the control of immune mechanisms involving antibody production, and cell-mediated forms of immunity such as delayed type hypersensitivity and transplantation immunity (1-5); there are, however, few published reports of their effect on the immune response to microorganisms despite infection being a serious complications of their use in clinical practice. The present report deals with the influence of some immunosuppressive drugs on the immune response to a facultative intracellular parasite.

Tuberculosis, brucellosis, listeriosis, and salmonellosis are examples of infections which give rise to a cell-mediated form of immunity which evolves through similar mechanisms (6); it is therefore logical to assume that observations on one host-parasite system will have relevance to the others. Listeriosis in the mouse has been chosen as a model for the present study because it offers several advantages. Firstly, the immune response sets in early and runs a short course, so that an immunosuppressive effect is quickly revealed; secondly, a Listeria infection, as assessed by bacterial enumeration, provides an accurate and quantitative assessment of immunity and the magnitude of the immunosuppressive effect obtained with drugs. Mice infected with a sublethal dose of Listeria monocytogenes develop an immune response which interrupts the growth of the organisms in vivo. The experiments to be described are based upon the premise the effective suppression of the immune response by drugs would result in continued multiplication of Listeria , particularly in the spleen and liver.

Four drugs, representing four different categories of cytotoxic agents, were chosen for study: (a) cyclophosphamide, a polyfunctional alkylating agent; (b) vinblastine, an antimitotic agent; (c) methotrexate, a folic acid anatagonist; and (d) azathioprine, a purine analogue. The present report deals with the effect of these four drugs on the immune response to Listeria infection in mice.

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