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Fungal and Parasitic Infections

Local Delivery of the Viral Interleukin-10 Gene Suppresses Tissue Inflammation in Murine Pneumocystis carinii Infection

Sanbao Ruan, Chandra Tate, Janet J. Lee, Thomas Ritter, Jay K. Kolls, Judd E. Shellito
Sanbao Ruan
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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Chandra Tate
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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Janet J. Lee
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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Thomas Ritter
2Institute of Medical Immunology, Humboldt University, Berlin, Germany
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Jay K. Kolls
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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Judd E. Shellito
1Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana
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  • For correspondence: jshell@lsuhsc.edu
DOI: 10.1128/IAI.70.11.6107-6113.2002
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  • FIG. 1.
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    FIG. 1.

    Concentration of endogenous IL-10 in lung tissue after P. carinii (PC) challenge. (A) Control and CD4-depleted mice were inoculated with P. carinii, and lung tissue was assayed for IL-10 at serial intervals. An additional control included mice inoculated with PBS. Each data point represents mean ± SD for at least five animals. (B) Fixed lung tissue was also examined and scored microscopically for intensity of infection. Data represent the mean results for at least three animals.

  • FIG. 2.
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    FIG. 2.

    Expression of the vIL-10 transgene after intrapulmonary injection. A given amount (109 PFU) of AdvIL-10 was injected intratracheally (i.t.), and vIL-10 was assayed by ELISA in bronchoalveolar lavage fluid and in serum at serial intervals. Each data point represents the mean of three animals.

  • FIG. 3.
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    FIG. 3.

    Experimental design. Gene transfer of AdvIL-10 or AdLuc. i.t., intratracheal; H&E, hematoxylin and eosin; PC, P. carinii; and GMS, Gomori-methenamine silver; IP, intrapulmonary.

  • FIG. 4.
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    FIG. 4.

    Lung tissue burden of P. carinii (PC) in mice pretreated with AdvIL-10 or AdLuc. Data are from mice sacrificed 4 weeks after inoculation with P. carinii. The two leftmost columns represent control (CD4+) mice, and the two rightmost columns represent CD4-depleted (CD4−) mice. Each data point represents mean ± SD for at least 10 animals. it, intratracheal.

  • FIG. 5.
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    FIG. 5.

    Effect of pretreatment with AdvIL-10 or AdLuc on tissue inflammation. Data are from mice sacrificed 4 weeks after inoculation with P. carinii. The two leftmost columns represent control mice, while the two rightmost columns represent CD4-depleted mice. Alveolar inflammatory scores were calculated by microscopic examination of hematoxylin- and eosin-stained lung tissue. Each data point represents mean ± SD for at least six animals. *, P < 0.05 in comparison to AdLuc.

  • FIG. 6.
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    FIG. 6.

    Experimental design. Immune reconstitution during P. carinii (PC) infection. i.p., intrapulmonary; BALF, bronchoalveolar lavage fluid.

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    FIG. 7.

    Effect of AdvIL-10 or AdLuc on parameters of tissue inflammation during immune reconstitution. (A) Lung wet weights 2 weeks after immune reconstitution in mice treated with AdvIL-10 or AdLuc. *, P < 0.05 in comparison to AdLuc. (B) Concentrations of LDH in bronchoalveolar lavage fluid 2 weeks after immune reconstitution in mice treated with AdvIL-10 or AdLuc. *, P < 0.01 in comparison to AdLuc. (C) Lavaged neutrophils 2 weeks after immune reconstitution in mice treated with AdvIL-10 or AdLuc. *, P < 0.05 in comparison to AdLuc.

  • FIG. 8.
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    FIG. 8.

    Survival after immune reconstitution in mice treated with AdvIL-10 or AdLuc. Survival was significantly improved (P < 0.05) in mice receiving AdvIL-10 compared to that in mice receiving AdLuc.

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Local Delivery of the Viral Interleukin-10 Gene Suppresses Tissue Inflammation in Murine Pneumocystis carinii Infection
Sanbao Ruan, Chandra Tate, Janet J. Lee, Thomas Ritter, Jay K. Kolls, Judd E. Shellito
Infection and Immunity Nov 2002, 70 (11) 6107-6113; DOI: 10.1128/IAI.70.11.6107-6113.2002

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Local Delivery of the Viral Interleukin-10 Gene Suppresses Tissue Inflammation in Murine Pneumocystis carinii Infection
Sanbao Ruan, Chandra Tate, Janet J. Lee, Thomas Ritter, Jay K. Kolls, Judd E. Shellito
Infection and Immunity Nov 2002, 70 (11) 6107-6113; DOI: 10.1128/IAI.70.11.6107-6113.2002
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KEYWORDS

Genetic Therapy
interleukin-10
Pneumonia, Pneumocystis

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