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Infection and Immunity, November 1998, p. 5286-5294, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Role of Liver NK Cells and Peritoneal Macrophages in Gamma Interferon and Interleukin-10 Production in Experimental Bacterial Peritonitis in Mice

Shuhji Seki,1,* Shun-ichi Osada,2 Satoshi Ono,2 Suefumi Aosasa,2 Yoshiko Habu,1 Tetsuro Nishikage,1 Hidetaka Mochizuki,2 and Hoshio Hiraide1

Division of Basic Traumatology, National Defense Medical College Research Institute,1 and First Department of Surgery, National Defense Medical College,2 Namiki, Tokorozawa 359-8513, Japan

Received 22 December 1997/Returned for modification 1 May 1998/Accepted 21 July 1998

Gamma interferon (IFN-gamma ), tumor necrosis factor alpha (TNF-alpha ), and interleukin-10 (IL-10) production by liver, spleen, lung, peripheral blood mononuclear cells (MNC), and peritoneal exudate cells (PEC) in experimental bacterial peritonitis was examined by cecum ligation and puncture (CLP) (with an 18-gauge needle) of BALB/c mice. MNC of organs were cultured for 18 h, and cytokine levels in supernatants were examined. Cytokines contained in peritoneal lavage fluid were regarded as those produced by PEC. Only liver MNC and PEC produced substantial amounts of IFN-gamma , and PEC were the main source of IL-10, especially 12 h after CLP. As reflected by the cytokine production by liver MNC and PEC, serum IFN-gamma and IL-10 levels were elevated after CLP. C57BL/6 (B6) mice and BALB/c nude mice showed a similar pattern of cytokine production. TNF-alpha levels in culture supernatants, peritoneal lavage fluid, and sera were not significantly elevated compared to those of sham-operated mice. In vivo depletion of NK cells of B6 mice with anti-asialo GM1 or anti-NK1.1 antibody greatly decreased IFN-gamma levels in liver MNC culture supernatants and sera, suggesting that liver NK cells are IFN-gamma producers. On the other hand, plastic-adherent PEC macrophages are the major IL-10 producers. Mice subjected to a cecum ligation and cut procedure (which have a more severe peritonitis) showed much higher IFN-gamma and IL-10 levels than those subjected to CLP, while mice subjected to CLP with a smaller (22-gauge) needle showed low levels of these cytokines. These findings show that liver NK cells and PEC macrophages are important for the production of proinflammatory and anti-inflammatory cytokines in bacterial peritonitis.

* Corresponding author. Mailing address: Division of Basic Traumatology, National Defense Medical College Research Institute, Namiki, Tokorozawa 359-8513, Japan. Phone: 81-429-95-1633. Fax: 81-429-91-1613. E-mail: btraums{at}ndmc.ac.jp.

Infection and Immunity, November 1998, p. 5286-5294, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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