IL-6 PRODUCED BY KUPFFER CELLS INDUCES STAT PROTEIN-ACTIVATION IN HEPATOCYTES EARLY DURING THE COURSE OF SYSTEMIC LISTERIAL INFECTIONS

Kupffer cells were the principal source of IL-6 produced in the livers of mice following i.v. inoculation of Listeria monocytogenes. IL-6 mR NA expression and the production of IL-6 were reduced drastically with in the nonparenchymal liver cell population derived from mice rendered Kupffer cell depleted by pretreatment with liposome-encapsulated dich loromethylene diphosphonate, A sharp increase in the appearance of act ivated STAT3 occurred in extracts of purified hepatocytes derived from normal mice infected i.v. with Listeria. Remarkably, the kinetics of this increase overlapped IL-6 mRNA expression by Kupffer cells; each p eaked at approximately 30 min postinfection, No increase in STAT3 acti vation,vas observed in IL-6 deficient or Kupffer cell-depleted animals . The results of these experiments indicate that the synthesis of IL-6 and the activation of STAT3 within hepatocytes are critical functions of Kupffer cells occurring very early during the course of systemic l isterial infections.