CYTOKINE EXPRESSION IN THE LIVER DURING THE EARLY PHASE OF MURINE TULAREMIA

Cytokine expression was determined in the livers of mice inoculated su bcutaneously with Francisella tularensis LVS, During the first 48 h of infection, there was a logarithmic increase of bacteria in the liver, with a doubling time of 2.5 h. Within 48 h, tumor necrosis factor alp ha (TNF-alpha), interleukin 10 (IL-10), IL,-12, and gamma interferon ( IFN gamma) mRNAs were expressed, and production of TNF-alpha and IFN-g amma was demonstrated. There was no expression within 96 h of mRNA fro m IL-2, IL-3, or IL-4. After subcutaneous inoculation of heat-killed L VS, no expression of any of the cytokine mRNAs and no increase in the levels of TNF-alpha or IFN-gamma occurred. The expression of TNF-alpha , IL-12, and IFN-gamma is held to be important to evoke an early T-cel l-independent host defense against F. tularensis as well as to drive t he expansion of a protective Th1 cell response.