Effects of cytokine gene therapy on particulate-induced inflammation in the murine air pouch

S. Sud; S. Y. Yang; C. H. Evans; P. D. Robbins; P. H. Wooley

doi:10.1023/A:1012898513512

Effects of cytokine gene therapy on particulate-induced inflammation in the murine air pouch

S. Sud, S. Y. Yang, C. H. Evans, P. D. Robbins, P. H. Wooley

Physical Medicine and Rehabilitation

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Retroviral vectors encoding the human IL-1 antagonist (IL-1Ra) gene and the human tumor necrosis factor soluble receptor (sTNF-R) gene were investigated using an in vivo model of the inflammatory response to orthopedic wear debris. Air pouches established in BALB/c mice were injected with polymethylmethacrylate (PMMA) particles to provoke an inflammatory reaction, and infected with retroviral vectors expressing IL-1Ra, sTNF-R or a LacZ marker gene. Pouch membranes and fluids were harvested after 48 or 72 hours for analyses. Positive PCR reactions for Neo genes were observed specifically in DNA extracted from the membrane of retroviral-infected pouches. ELISA assays revealed the presence of human IL-1Ra in pouch fluid from DFG-IRAP-Neo transduced mice, but not control animals. Histological evaluation indicated that the IL-1Ra gene transfer was associated with markedly decreased inflammation in the model, with resolution of the edematous phase of the reaction, decreased pouch fluid accumulation, and lowered macrophage influx. The data suggest that the air pouch model represents a useful tool to evaluate gene therapy, and demonstrate that IL-1Ra gene therapy may be an appropriate therapeutic approach to inflammation.

Original language	English (US)
Pages (from-to)	361-372
Number of pages	12
Journal	Inflammation
Volume	25
Issue number	6
DOIs	https://doi.org/10.1023/A:1012898513512
State	Published - 2001

Keywords

Air pouch
Gene therapy
IL-1Ra
PMMA

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1023/A:1012898513512

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title = "Effects of cytokine gene therapy on particulate-induced inflammation in the murine air pouch",

abstract = "Retroviral vectors encoding the human IL-1 antagonist (IL-1Ra) gene and the human tumor necrosis factor soluble receptor (sTNF-R) gene were investigated using an in vivo model of the inflammatory response to orthopedic wear debris. Air pouches established in BALB/c mice were injected with polymethylmethacrylate (PMMA) particles to provoke an inflammatory reaction, and infected with retroviral vectors expressing IL-1Ra, sTNF-R or a LacZ marker gene. Pouch membranes and fluids were harvested after 48 or 72 hours for analyses. Positive PCR reactions for Neo genes were observed specifically in DNA extracted from the membrane of retroviral-infected pouches. ELISA assays revealed the presence of human IL-1Ra in pouch fluid from DFG-IRAP-Neo transduced mice, but not control animals. Histological evaluation indicated that the IL-1Ra gene transfer was associated with markedly decreased inflammation in the model, with resolution of the edematous phase of the reaction, decreased pouch fluid accumulation, and lowered macrophage influx. The data suggest that the air pouch model represents a useful tool to evaluate gene therapy, and demonstrate that IL-1Ra gene therapy may be an appropriate therapeutic approach to inflammation.",

keywords = "Air pouch, Gene therapy, IL-1Ra, PMMA",

author = "S. Sud and Yang, {S. Y.} and Evans, {C. H.} and Robbins, {P. D.} and Wooley, {P. H.}",

note = "Funding Information: Acknowledgements—The authors gratefully acknowledge the contributions of W. Dwayne Lawrence, M.D. and the Pathology Image Analysis Laboratory at Hutzel Hospital, the histological expertise of Lois Mayton, the technical support of Dr. Janey D. Whalen, and grant support from the Veterans Administration (Rehabilitation Study Section) and the Arthritis Foundation.",

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doi = "10.1023/A:1012898513512",

language = "English (US)",

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pages = "361--372",

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AU - Sud, S.

AU - Yang, S. Y.

AU - Evans, C. H.

AU - Robbins, P. D.

AU - Wooley, P. H.

N1 - Funding Information: Acknowledgements—The authors gratefully acknowledge the contributions of W. Dwayne Lawrence, M.D. and the Pathology Image Analysis Laboratory at Hutzel Hospital, the histological expertise of Lois Mayton, the technical support of Dr. Janey D. Whalen, and grant support from the Veterans Administration (Rehabilitation Study Section) and the Arthritis Foundation.

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N2 - Retroviral vectors encoding the human IL-1 antagonist (IL-1Ra) gene and the human tumor necrosis factor soluble receptor (sTNF-R) gene were investigated using an in vivo model of the inflammatory response to orthopedic wear debris. Air pouches established in BALB/c mice were injected with polymethylmethacrylate (PMMA) particles to provoke an inflammatory reaction, and infected with retroviral vectors expressing IL-1Ra, sTNF-R or a LacZ marker gene. Pouch membranes and fluids were harvested after 48 or 72 hours for analyses. Positive PCR reactions for Neo genes were observed specifically in DNA extracted from the membrane of retroviral-infected pouches. ELISA assays revealed the presence of human IL-1Ra in pouch fluid from DFG-IRAP-Neo transduced mice, but not control animals. Histological evaluation indicated that the IL-1Ra gene transfer was associated with markedly decreased inflammation in the model, with resolution of the edematous phase of the reaction, decreased pouch fluid accumulation, and lowered macrophage influx. The data suggest that the air pouch model represents a useful tool to evaluate gene therapy, and demonstrate that IL-1Ra gene therapy may be an appropriate therapeutic approach to inflammation.

AB - Retroviral vectors encoding the human IL-1 antagonist (IL-1Ra) gene and the human tumor necrosis factor soluble receptor (sTNF-R) gene were investigated using an in vivo model of the inflammatory response to orthopedic wear debris. Air pouches established in BALB/c mice were injected with polymethylmethacrylate (PMMA) particles to provoke an inflammatory reaction, and infected with retroviral vectors expressing IL-1Ra, sTNF-R or a LacZ marker gene. Pouch membranes and fluids were harvested after 48 or 72 hours for analyses. Positive PCR reactions for Neo genes were observed specifically in DNA extracted from the membrane of retroviral-infected pouches. ELISA assays revealed the presence of human IL-1Ra in pouch fluid from DFG-IRAP-Neo transduced mice, but not control animals. Histological evaluation indicated that the IL-1Ra gene transfer was associated with markedly decreased inflammation in the model, with resolution of the edematous phase of the reaction, decreased pouch fluid accumulation, and lowered macrophage influx. The data suggest that the air pouch model represents a useful tool to evaluate gene therapy, and demonstrate that IL-1Ra gene therapy may be an appropriate therapeutic approach to inflammation.

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Effects of cytokine gene therapy on particulate-induced inflammation in the murine air pouch

Abstract

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