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Infection and Immunity, May 2008, p. 2130-2137, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.00065-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Interleukin-12 and Host Defense against Murine Pneumocystis Pneumonia{triangledown}

Sanbao Ruan,1 Laura McKinley,2 Mingquan Zheng,2 Xiaowen Rudner,1 Alain D'Souza,1 Jay K. Kolls,2 and Judd E. Shellito1*

Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana,1 Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania2

Received 16 January 2008/ Returned for modification 23 February 2008/ Accepted 1 March 2008

Little is known about the role of the cytokine interleukin-12 (IL-12) in Pneumocystis pneumonia or its potential use as immunotherapy. We asked whether release of IL-12 is part of the normal host response to this infection and whether local treatment with IL-12 or gene transfer of IL-12 could accelerate clearance of infection. IL-12 was assayed by enzyme-linked immunosorbent assay in normal mice and in mice deficient in IL-12 after inoculation of Pneumocystis carinii. P. carinii-infected mice were treated with local instillation of IL-12 and gene transfer of the IL-12 gene. Inoculation of P. carinii into normal mice evoked a brisk release of IL-12 into lung tissue, and IL-12 P35-deficient mice showed delayed clearance of infection measured by PCR for P. carinii rRNA. In control mice, intranasal recombinant IL-12 accelerated clearance of infection, and this was associated with increased recruitment of inflammatory cells into lavage fluid and increased release of tumor necrosis factor alpha, IL-12, and gamma interferon. Similar results were observed in infected mice depleted of CD4+ lymphocytes by using in vivo transfer of the IL-12 gene in a replication-deficient adenoviral vector. IL-12 is part of the normal host response to infection with P. carinii. IL-12 therapy can enhance host resistance to infection in both normal mice and mice depleted of CD4+ T lymphocytes. A treatment effect of IL-12 is mediated through enhanced inflammatory cell recruitment into lung tissue and increased tissue concentrations of proinflammatory cytokines.

* Corresponding author. Mailing address: LSU Health Sciences Center, 1901 Perdido Street, Suite 3205, New Orleans, LA 70112. Phone: (504) 568-4634. Fax: (504) 568-4295. E-mail: jshell{at}lsuhsc.edu

{triangledown} Published ahead of print on 10 March 2008.

Editor: A. Casadevall

Infection and Immunity, May 2008, p. 2130-2137, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.00065-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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