Immunomodulatory therapy using recombinant IFN-γ revealed opposite effects in different stages of experimental murine membranous nephropathy

Jin Shuen Chen, Cai Mei Zheng, Ching Feng Huang, Shih Hua Lin, Pauling Chu, Huey Kang Sytwu, Yuh Feng Lin, Chia Chao Wu

Research output: Contribution to journalArticle

Abstract

Background: Therapeutic agents for membranous nephropathy (MN) remain ill-defined. Strongly Th2 polarized immune response participated in the pathogenesis of MN. Here, we assessed the therapeutic effects and mechanisms of Th1 cytokine, IFN-γ, therapy for experimental murine MN. Methods: MN was induced in BALB/c mice with intravenous injections of cationic bovine serum albumin. Three groups of mice were administered 50 μg/kg recombinant IFN-γ in the early stage (weeks 1 to 3), late stage (weeks 4 to 6) or PBS (weeks 1 to 6) intravenously three times a week starting from MN induction. Disease severity was verified by serum and urine metabolic profiles and by renal histopathology. The oxidative stress was measured by superoxide production using DHE stain while inflammatory status was measured by positive NF-κB cells. Th1/Th2 cell axis polarizations were also determined. Results: There were significant reduction of proteinuria, remarkable amelioration of glomerular lesions accompanied by decreased immune deposition, and complement activation in mice receiving rIFN-γ therapy in the early stage. The mice receiving rIFN-γ therapy in the late stage revealed deterioration of metabolic and renal histopathological parameters. Similarly, changes of inflammatory status, and oxidative stress also showed opposite patterns. Early rIFN-γ therapy may reverse the strongly Th2 immune response of MN to alleviate disease severity, while late rIFN-γ therapy exacerbated the inflammatory process of MN, resulting in greater disease severity. Conclusions: There were opposite effects of rIFN-γ therapy in different stages of MN. Immunomodulatory treatment using rIFN-γ in the early stage of MN shifts the Th1/Th2 immune response and may be considered as a potential therapeutic strategy of MN in the future.

Original languageEnglish
Pages (from-to)287-295
Number of pages9
JournalJournal of Medical Sciences (Taiwan)
Volume32
Issue number6
Publication statusPublished - 2012

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Membranous Glomerulonephritis
Immunomodulation
Therapeutics
Oxidative Stress
Kidney
Th2 Cells
Th1 Cells
Investigational Therapies
Metabolome
Complement Activation
Therapeutic Uses
Bovine Serum Albumin
Secondary Prevention
Proteinuria
Intravenous Injections
Superoxides
B-Lymphocytes
Coloring Agents
Urine
Cytokines

Keywords

  • IFN-γ
  • Immunomodulatory therapy
  • Membranous nephropathy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Immunomodulatory therapy using recombinant IFN-γ revealed opposite effects in different stages of experimental murine membranous nephropathy. / Chen, Jin Shuen; Zheng, Cai Mei; Huang, Ching Feng; Lin, Shih Hua; Chu, Pauling; Sytwu, Huey Kang; Lin, Yuh Feng; Wu, Chia Chao.

In: Journal of Medical Sciences (Taiwan), Vol. 32, No. 6, 2012, p. 287-295.

Research output: Contribution to journalArticle

Chen, Jin Shuen ; Zheng, Cai Mei ; Huang, Ching Feng ; Lin, Shih Hua ; Chu, Pauling ; Sytwu, Huey Kang ; Lin, Yuh Feng ; Wu, Chia Chao. / Immunomodulatory therapy using recombinant IFN-γ revealed opposite effects in different stages of experimental murine membranous nephropathy. In: Journal of Medical Sciences (Taiwan). 2012 ; Vol. 32, No. 6. pp. 287-295.
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abstract = "Background: Therapeutic agents for membranous nephropathy (MN) remain ill-defined. Strongly Th2 polarized immune response participated in the pathogenesis of MN. Here, we assessed the therapeutic effects and mechanisms of Th1 cytokine, IFN-γ, therapy for experimental murine MN. Methods: MN was induced in BALB/c mice with intravenous injections of cationic bovine serum albumin. Three groups of mice were administered 50 μg/kg recombinant IFN-γ in the early stage (weeks 1 to 3), late stage (weeks 4 to 6) or PBS (weeks 1 to 6) intravenously three times a week starting from MN induction. Disease severity was verified by serum and urine metabolic profiles and by renal histopathology. The oxidative stress was measured by superoxide production using DHE stain while inflammatory status was measured by positive NF-κB cells. Th1/Th2 cell axis polarizations were also determined. Results: There were significant reduction of proteinuria, remarkable amelioration of glomerular lesions accompanied by decreased immune deposition, and complement activation in mice receiving rIFN-γ therapy in the early stage. The mice receiving rIFN-γ therapy in the late stage revealed deterioration of metabolic and renal histopathological parameters. Similarly, changes of inflammatory status, and oxidative stress also showed opposite patterns. Early rIFN-γ therapy may reverse the strongly Th2 immune response of MN to alleviate disease severity, while late rIFN-γ therapy exacerbated the inflammatory process of MN, resulting in greater disease severity. Conclusions: There were opposite effects of rIFN-γ therapy in different stages of MN. Immunomodulatory treatment using rIFN-γ in the early stage of MN shifts the Th1/Th2 immune response and may be considered as a potential therapeutic strategy of MN in the future.",
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AU - Sytwu, Huey Kang

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AB - Background: Therapeutic agents for membranous nephropathy (MN) remain ill-defined. Strongly Th2 polarized immune response participated in the pathogenesis of MN. Here, we assessed the therapeutic effects and mechanisms of Th1 cytokine, IFN-γ, therapy for experimental murine MN. Methods: MN was induced in BALB/c mice with intravenous injections of cationic bovine serum albumin. Three groups of mice were administered 50 μg/kg recombinant IFN-γ in the early stage (weeks 1 to 3), late stage (weeks 4 to 6) or PBS (weeks 1 to 6) intravenously three times a week starting from MN induction. Disease severity was verified by serum and urine metabolic profiles and by renal histopathology. The oxidative stress was measured by superoxide production using DHE stain while inflammatory status was measured by positive NF-κB cells. Th1/Th2 cell axis polarizations were also determined. Results: There were significant reduction of proteinuria, remarkable amelioration of glomerular lesions accompanied by decreased immune deposition, and complement activation in mice receiving rIFN-γ therapy in the early stage. The mice receiving rIFN-γ therapy in the late stage revealed deterioration of metabolic and renal histopathological parameters. Similarly, changes of inflammatory status, and oxidative stress also showed opposite patterns. Early rIFN-γ therapy may reverse the strongly Th2 immune response of MN to alleviate disease severity, while late rIFN-γ therapy exacerbated the inflammatory process of MN, resulting in greater disease severity. Conclusions: There were opposite effects of rIFN-γ therapy in different stages of MN. Immunomodulatory treatment using rIFN-γ in the early stage of MN shifts the Th1/Th2 immune response and may be considered as a potential therapeutic strategy of MN in the future.

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