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.
|Number of pages||9|
|Journal||Journal of Medical Sciences (Taiwan)|
|Publication status||Published - 2012|
- Immunomodulatory therapy
- Membranous nephropathy
ASJC Scopus subject areas