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Infect. Immun. doi:10.1128/IAI.00065-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Interleukin-12 and Host Defense against Murine Pneumocystis Pneumonia

Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, LA; Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA

^* To whom correspondence should be addressed. Email: jshell{at}lsuhsc.edu.

	Abstract

Rationale: Little is known about the role of the cytokine IL-12 in Pneumocystis pneumonia or its potential use as immunotherapy.

Objectives: 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.

Methods: IL-12 was assayed by ELISA in normal mice and in mice deficient in IL-12 after inoculation of P. carinii. P. carinii-infected mice were treated with local instillation of IL-12 and gene transfer of the IL-12 gene.

Measurements and Main Results: 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 as PCR for P. carinii ribosomal RNA. 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 TNF-, IL-12, and IFN-. Similar results were observed in infected mice depleted of CD4+ lymphocytes using in vivo transfer of the IL-12 gene in a replication deficient adenoviral vector.

Conclusions: 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.