The Effect of Listeria Monocytogenes Priming on the Gamma Interferon Response in Cytomegalovirus-Infected Mice
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Gamma interferon has antiviral, antitumor, and immunoregulatory properties. One current area of research in which the activity of interferon is being explored is that of recurrent herpesvirus infection. Various agents known to induce production of interferon are being tested in several experimental herpesvirus inifections of murine systems, with respect to their possible clinical application in human herpesvirus infections. The following investigation involved the use of a bacterial agent, Listeria monocytogenes, in an attempt to induce high levels of gamma interferon by mitogenic stimulation of spleen cell cultures from cytomegalovirus-infected mice. An experimental murine cytomegalovirus (CMV) infection was established by intraperitoneal inoculation with 10 5 pfu MCMV per animal. The virus was titrated by measurement of infectious virus associated with salivary gland tissue, as indicated by coculture with syngeneic mouse embryonic fibroblasts. This provided a comparison of virus levels in CMV-infected animals that either had or had not received 5xl0 3 Listeria m. inocula six to seven days before sacrifice. Gamma interferon production by spleen cell cultures from both these and non-virally infected controls was noted, using the viral plaque reduction assay. Although several agents known to induce in vitro interferon production were used in spleen cell culture treatment, only the combination of two non-specific mitogens phytohemagglutinin and concanavalin A was effective in induction of measurable levels of interferon. Furthermore, Listeria treatment of virally infected animals was correlated with a depression of gamma interferon production, in comparison with that in CMV-infected animals. Listeria treatment throughout the experiment was also correlated with an increase in spleen cell number per animal, thus indicating enhancement of lymphoproliferation.