Enhancement of resistance to Listeria monocytogenes infection in mice by pyrimidine analogs.
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.
D000818:Animals; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007369:Interferon Inducers / Q000627:therapeutic use*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000627:therapeutic use*
D007369:Interferon Inducers; D011743:Pyrimidines; C014927:2-amino-5-bromo-6-methyl-4-pyrimidinol; C033561:2-amino-5-iodo-6-phenyl-4-pyrimidinone; D003596:Cytosine; C033560:bropirimine