CYTOKINE MESSENGER-RNA EXPRESSION IN LIVERS OF MICE INFECTED WITH LISTERIA-MONOCYTOGENES

Temporally distinct groups of cytokine expression were observed by rev erse transcription-polymerase chain reaction assay, in situ hybridizat ion, and immunohistochemistry in the livers of Listeria monocytogenes- infected mice. One group consisted of interferon-gamma (IFN-gamma), tu mor necrosis factor alpha (TNF-alpha), and interleukin-10 (IL-10), for which mRNAs were induced within 1 day after challenge. A second group consisted of IL-2 and IL-4, for which mRNA was strongly expressed at 1 day but then suppressed at 3 days into the infection. Granulocyte-ma crophage colony-stimulating factor (GM-CSF), IL-1alpha, and IL-6 mRNA constituted a third group, which was increased at 3 days after challen ge. Distributions of cytokine mRNA-expressing cells in the liver was o bserved by in situ hybridization. Cells expressing TNF-alpha and IL-1a lpha mRNA were present throughout liver granulomas. whereas cells that expressed IFN-gamma mRNA were observed mostly along the periphery of granulomas. Cells expressing IL-2, IL-4, IL-6, IL-10, and GM-CSF mRNA were distributed principally in the hepatic sinuses. Cells expressing IL-10 mRNA increased in number early in the infection when L. monocyto genes was multiplying in the liver. We conclude that cytokine mRNA exp ression during the early phases of L. monocytogenes infection in mice is temporally regulated and that IFN-gamma, TNF-alpha, and IL-1alpha a re expressed by cells associated with hepatic granulomas.