The modulation of murine host resistance to
infection with Listeria monocytogenes by the substituted
pyrimidine anti-viral compounds,
2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP), 2-amino-5-bromo-6-phenyl-4-pyrimidinol (ABPP) and 2-amino-5-iodo-6-phenyl-4-pyrimidinol (
AIPP) was investigated. BAF1 mice given three daily
injections of ABMP, ABPP (as well as of the
interferon-inducer
poly I:C) demonstrated enhanced anti-listerial resistance, as measured by a 100-fold increase in the median lethal dose of Listeria compared to vehicle-treated control mice. This enhancement was also detectable as a decrease (up to 100-fold) in the number of viable Listeria recoverable from the livers and spleens of mice during the non-immune phase of natural resistance (24-72 h following
infection) to this pathogen. In contrast,
AIPP did not enhance anti-listerial resistance. Since each of the effective agents have been shown to induce the production of
interferon, the role of
interferon in the mechanism of natural resistance to Listeria was evaluated. The serum of untreated B10.A mice infected with Listeria was shown to contain high levels of
interferon. Treatment of these mice with a potent anti-mouse
interferon antibody preparation completely neutralized circulating
interferon activity; however, such treatment had no apparent effect on the growth of Listeria. In addition, mice which received
injections of both ABMP and anti-
interferon demonstrated a level of resistance identical to that seen in mice given ABMP and normal serum. Based on these results, we propose that although
interferon is produced in response to listerial
infection,
interferon is not a critically important mediator in the mechanism of natural resistance to this pathogen. Furthermore, it appears that the immunomodulating activity of these experimental compounds does not involve
interferon.