Interferon: Friend or Foe?

Tang, Rosa A.

doi:10.1001/archopht.1995.01100080037026

Cited by 9 publications

(3 citation statements)

References 5 publications

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“…This darker side of IFN activity has been recognized by various investigators and was summarized in an editorial by Tang, who had asked the important question ‘Interferon: friend or foe ? '[5]. …”

Section: Introductionsupporting

confidence: 40%

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Fabrizi

Aghemo

Fogazzi

et al. 2013

Kidney Blood Press Res

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Background/Aims: Interferon treatment of malignant or viral diseases can be accompanied by various side-effects including nephro-toxicity. Methods: We report on a 68-year-old Caucasian male who received dual therapy with pegylated interferon 2a plus ribavirin for chronic hepatitis C. Results: After three months of antiviral therapy, the patient developed acute kidney failure (serum creatinine up to 6 mg/dL) with mild proteinuria (500 mg daily) and haematuria. Immediate immunosuppressive therapy with high-dose intravenous steroids did not improve kidney function. Kidney biopsy was consistent with acute tubular necrosis without glomerular abnormalities. He started long-term peritoneal dialysis (four regular exchanges) to provide both dialysis adequacy and ascites removal. Kidney function gradually improved over the following months (serum creatinine around 2 mg/dL) and peritoneal dialysis was continued with two exchanges daily. The temporal relationship between the administration of the drug and the occurrence of nephro-toxicity, and the absence of other obvious reasons for acute tubular necrosis support a causative role for pegylated interferon; benefit on kidney disease was noted after withdrawal of antiviral agents. An extensive review of the literature on acute tubular necrosis associated with interferon-based therapy, based on in vitro data and earlier case-reports, has been made. The proposed pathogenic mechanisms are reviewed. Conclusions: Our case emphasizes the importance of monitoring renal function during treatment of chronic hepatitis C with antiviral combination therapy as treatment may precipitate kidney damage at tubular level.

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Section: Introductionsupporting

confidence: 40%

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Fabrizi

Aghemo

Fogazzi

et al. 2013

Kidney Blood Press Res

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“…IFNs belong to the family of cytokines, which have an antiviral effect, antiproliferative effect, and immunomodulatory effects (Sen & Ransohoff, ). IFNA1, as one of the interferons, has been widely reported to have antiviral action and affects the adaptive immune response, which is involving dendritic cells and NK cells, as well as lymphocytes (Platanias, ; Tang, ). Santos et al () investigated that upregulation of the IFNAR1 gene and downregulation of IFNA1 might have a function on the pathogenesis of chronic infection.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1

Yang

Zhang

Qian

et al. 2018

Journal Cellular Physiology

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Osteoarthritis (OA) is the most common disease of arthritis, a chronic joint disease that is always correlated with massive destruction such as cartilage destruction, inflammation of the synovial membrane, and so on. This study aims to explore the role of long noncoding RNA (lncRNA) LOC101928134 in the synovial hyperplasia and cartilage destruction, more specifically, in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in an OA rat model. Microarray‐based gene expression analysis was conducted to screen out the lncRNA differentially expressed in OA and predict the target gene of the lncRNA with the involvement of the signaling pathway through Kyoto encyclopedia of genes and genomes (KEGG) analysis. A model of OA was established and treated with the small interfering RNA LOC101928134/inhibitor of JAK/STAT signaling pathway to investigate the relationship among LOC101928134, IFNA1, and the JAK/STAT signaling pathway in OA. The effect of LOC101928134 on the serum levels of IFNA1, interleukin‐1β, and tumor necrosis factor‐α, and the apoptosis of synovial and cartilage cells was evaluated. LOC101928134, which was found to be highly expressed in knee joint synovial tissues of OA rats, regulated the expression of IFNA1 gene and inhibited JAK/STAT signaling pathway. Downregulation of LOC101928134 resulted in reduced knee joint synovitis, relived inflammatory damage, and knee joint cartilage damage of OA rats. Besides, synovial cell apoptosis was enhanced upon LOC101928134 downregulation, while cartilage cell apoptosis of OA rats was suppressed. These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of OA rats via activation of JAK/STAT signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.

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“…Besides milder effects such as flu-like symptoms (nausea, fever, fatigue, myalgia, decreased concentration, anorexia, chills), high doses of IFNa may induce critical illness through a huge range of multi organ-dysfunction or a capillary-leak-syndrome which may be life-threatening (7,8). One of the organs concerned is the kidney, where IFNa can induce renal dysfunction manifested by lowered glomerular filtration rate (GFR) and increased proteinuria (9,10).…”

Section: Introductionmentioning

confidence: 99%

INTERFERON α2b INCREASES PARACELLULAR PERMEABILITY OF RENAL PROXIMAL TUBULAR LLC-PK₁CELLS VIA A MITOGEN ACTIVATED PROTEIN KINASE SIGNALING PATHWAY

Lechner

Pfaller

2001

Renal Failure

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The therapeutic administration of Interferon alpha2b (IFNalpha) is often accompanied by impaired renal function, i.e. reduced glomerular filtration rate and sometimes a so-called "capillary leak syndrome". To clarify the mechanism behind the renal dysfunction, confluent monolayers of LLC-PK1 cells were used as a model system to analyze the effects of IFNalpha on renal tubular epithelium. Examination of epithelial barrier function via measurement of transepithelial resistance (TER) revealed a dose dependent increase in paracellular permeability by IFNalpha treatment. The effect was reversible upon removal of IFNalpha at doses up to 5 x 10(3) U/mL. Apical or basolateral application of IFNalpha yielded the same decrease in TER. Tyrphostin A25, an inhibitor of phosphotyrosine kinases, ameliorated the IFNalpha induced decrease of TER. In order to unravel intracellular signal transduction pathways that may mediate IFNalpha induced changes of epithelial barrier function, we inhibited IFNalpha signaling through a mitogen activated protein kinase pathway by the Mek1 inhibitor PD98059. The inhibitor could be shown to prevent IFNalpha induced decrease of transepithelial resistance. Inhibitors of the p38 mitogen activated protein kinase pathway did not affect IFNalpha mediated changes of epithelial barrier function, indicating a highly specific role for the Mek/Erk pathway. Activation of mitogen activated protein kinase pathways by epidermal growth factor or anisomycin could not, per se, imitate the effect of IFNalpha on the paracellular permeability of LLC-PK1 monolayers. These findings provide evidence that IFNalpha can affect barrier function in renal epithelial cells via activation of the Mek/Erk pathway.

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Interferon: Friend or Foe?

Cited by 9 publications

References 5 publications

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1

INTERFERON α2b INCREASES PARACELLULAR PERMEABILITY OF RENAL PROXIMAL TUBULAR LLC-PK₁CELLS VIA A MITOGEN ACTIVATED PROTEIN KINASE SIGNALING PATHWAY

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Interferon: Friend or Foe?

Cited by 9 publications

References 5 publications

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Acute Tubular Necrosis Following Interferon-Based Therapy for Hepatitis C: Case Study with Literature Review

Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1

INTERFERON α2b INCREASES PARACELLULAR PERMEABILITY OF RENAL PROXIMAL TUBULAR LLC-PK1CELLS VIA A MITOGEN ACTIVATED PROTEIN KINASE SIGNALING PATHWAY

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INTERFERON α2b INCREASES PARACELLULAR PERMEABILITY OF RENAL PROXIMAL TUBULAR LLC-PK₁CELLS VIA A MITOGEN ACTIVATED PROTEIN KINASE SIGNALING PATHWAY