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Cancer Immunology, Immunotherapy

, Volume 34, Issue 3, pp 150–156 | Cite as

Endogenous interferon α/β produced by Kupffer cells inhibits interleukin-1, tumor necrosis factor α production and interleukin-2-induced activation of nonparenchymal liver cells

  • Shie-Pon Tzung
  • Stefan A. Cohen
Original articles

Summary

We have previously reported liver-specific interferon (IFN) α/β production by murine Kupffer cells that was not observed with other tissue macrophages incubated in the absence of stimulators such as IFNγ or lipopolysaccharide (LPS). Consequently, while interleukin-2 (IL-2) alone induced pronounced lymphokine-activated killer (LAK) activity from splenocytes, combination of anti-IFNα/β antibody with IL-2 was required to generate significant LAK activity from nonparenchymal liver cells. This endogenous IFNα/β production by Kupffer cells was not induced by LPS because (a) addition of polymyxin B did not abolish the positive effects of anti-IFNα/β antibody on nonparenchymal liver cells, and (b) similar results were obtained when comparing the responses of LPS-responsive C3HeB/FeJ and LPS-hyporesponsive C3H/HeJ mice. The possibility of hepatotropic infection was also ruled out in that anti-IFNα/β antibody enhanced hepatic but not splenic LAK cell induction in vitro in both conventional and germfree C3H/HeN mice. IFNα/β played an autoregulatory role by down-regulating the production of IL-1 and tumor necrosis factor α by Kupffer cells. However, the augmenting effect of anti-IFNα/β antibody on LAK induction from non-parenchymal liver cells was not mediated through an increase in the level of either IL-1 or TNFα, as specific antisera against either cytokine did not abrogate this positive effect. Finally, flow-cytometry analysis showed that IFNα/β significantly diminished the expression of IL-2 receptor α chain, indicating an inhibition of LAK cell generation at a relatively early stage of induction.

Key words

Kupffer cells Interferon α/β LAK cells 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Shie-Pon Tzung
    • 1
  • Stefan A. Cohen
    • 1
  1. 1.Department of Medicine, Division of Gastroenterology and HepatologyVeterans Administration Medical Center, and Buffalo General Hospital, State University of New York at BuffaloBuffaloUSA

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