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Infection and Immunity, June 2003, p. 3058-3067, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3058-3067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Stimulation of Hematopoiesis by the Fms-Like Tyrosine Kinase 3 Ligand Restores Bacterial Induction of Th1 Cytokines in Thermally Injured Mice

Tracy E. Toliver-Kinsky,1,2* Cheng Y. Lin,1 David N. Herndon,2,3 and Edward R. Sherwood1,2

Department of Anesthesiology,1 Department of Surgery, The University of Texas Medical Branch,3 Shriners Hospital for Children-Galveston Burns Unit, Galveston, Texas2

Received 11 October 2002/ Returned for modification 11 December 2002/ Accepted 12 February 2003

Patients with large burn injuries are susceptible to opportunistic infections due to impaired functions of multiple effector cells of innate immunity and acquired immunity, including macrophages, dendritic cells (DC), natural killer (NK) cells, and T cells. The ability of a host to produce Th1 cytokines, such as gamma interferon (IFN-{gamma}) and interleukin-12 (IL-12), upon infectious challenge is also impaired after burn injury. Stimulation of hematopoiesis, to regenerate new immune cells, may be an effective strategy for improving resistance to infections after severe burn trauma. Fms-like tyrosine kinase 3 ligand (Flt3L) is a hematopoietic cytokine that stimulates the expansion and differentiation of NK cells and DC. Using a mouse model, we tested the hypothesis that Flt3L treatments after burn injury stimulate the production of functional effector cells of innate immunity and restore appropriate Th1 cytokine responses to Pseudomonas aeruginosa, a common source of pneumonia and wound infections in burn victims. Flt3L increased splenic cellularity in sham (uninjured) and burned mice and increased the numbers of NK cells (DX5+) and DC (CD11c+). In response to P. aeruginosa, significant increases in the serum IFN-{gamma} levels and the numbers of splenic IFN-{gamma}-producing DC, NK cells, and T cells were observed in Flt3L-treated burned mice compared to the values obtained for untreated burned mice. The splenic levels of IL-12 and IL-15 mRNAs and the IL-12 and IL-15 receptors were also increased. In addition, Flt3L treatment restored the ability of splenic cultures prepared from burned mice to produce IFN-{gamma} and IL-12 after in vitro challenge with P. aeruginosa. Flt3L may have potential for restoring NK cell and DC functions and improving immunity after burn injury.

* Corresponding author. Mailing address: Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0591. Phone: (409) 770-6514. Fax: (409) 772-6371. E-mail: ttoliver{at}utmb.edu.

Editor: F. C. Fang

Infection and Immunity, June 2003, p. 3058-3067, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3058-3067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kawasaki, T., Choudhry, M. A., Schwacha, M. G., Bland, K. I., Chaudry, I. H. (2009). Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage. Am. J. Physiol. Cell Physiol. 296: C124-C130 [Abstract] [Full Text]  
  • Bohannon, J., Cui, W., Cox, R., Przkora, R., Sherwood, E., Toliver-Kinsky, T. (2008). Prophylactic Treatment with Fms-Like Tyrosine Kinase-3 Ligand after Burn Injury Enhances Global Immune Responses to Infection. J. Immunol. 180: 3038-3048 [Abstract] [Full Text]  
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