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Restoration of Natural IgM Production from Liver B Cells by Exogenous IL-18 Improves the Survival of Burn-Injured Mice Infected with Pseudomonas aeruginosa¹

Manabu Kinoshita^*, Nariyoshi Shinomiya, Satoshi Ono, Hironori Tsujimoto, Toshinobu Kawabata, Atsushi Matsumoto, Hoshio Hiraide^* and Shuhji Seki^2,

^* Division of Basic Traumatology, National Defense Medical College Research Institute, Tokorozawa, Japan; and Department of Immunology and Microbiology and Department of Surgery I, National Defense Medical College, Tokorozawa, Japan

Pseudomonas aeruginosa is the most common bacterium of postburn infection. In the present study we investigated the immune mechanism of susceptibility to this type of postburn infection and also examined the efficacy of IL-18 treatment. C57BL/6 mice were challenged with P. aeruginosa on day 7 after burn injury. Although the burn-injured mice showed a poor survival rate after bacterial challenge, they retained their IFN- production. The burned mice showed lower serum IgM levels and a poor IgM response following P. aeruginosa challenge in comparison with the sham mice, whereas IL-18 treatment after burn injury (alternate day injections for 1 wk) greatly improved the serum IgM levels, which are P. aeruginosa-independent natural IgM before bacterial challenge, thereby increasing the survival rate after the challenge. IL-18 treatment also induced specific IgM to P. aeruginosa in the sera 5 days after bacterial challenge in the burned mice. Interestingly, CD43⁺CD5^–CD23^–B220^dim cells, namely B-1b cells, increased in the liver after the IL-18 treatment and were found to actively produce IgM in vitro without any additional stimulation. Furthermore, the IL-18 treatment up-regulated the neutrophil count and the C3a levels in the blood as a result of the increased IgM level, which may thus play a critical role in the opsonization and elimination of any invading bacteria. IL-18 treatment for the burned mice and their resultant natural IgM production were thus found to strengthen the host defense against P. aeruginosa infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by a Grant-in-Aid for Special Research (Host Stress Responses to Internal and External Factors) from the National Defense Medical College (to N.S. and S.S.).

² Address correspondence and reprint requests to Dr. Shuhji Seki, Department of Immunology and Microbiology, National Defense Medical College, Namiki 3-2, Tokorozawa 359-8513, Japan. E-mail address: btraums{at}res.ndmc.ac.jp

³ Abbreviations used in this paper: MNC, mononuclear cell; AGM1, anti-asialo GM1; ALT, alanine aminotransferase; IVIG, intravenous Ig.