Attempts at suppression of amyloidogenesis in a mouse model by a variety of anti-inflammatory agents

Shmuel Shtrasburg, Mordechai Pras, Einat Rabinovich, Rivka Gal, Avi Livneh, Merav Lidar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The mainstay of AA amyloidosis prevention and treatment is suppression of inflammation. In the present study we have tried to determine the efficacy of a variety of anti-inflammatory agents at suppressing AA amyloidosis in a mouse model of the disease. Methods: AA amyloidosis was induced in Swiss male mice using amyloid enhancing factor and AgNO3. Suppression of amyloid formation was studied in comparison to saline, using i.p. injections of several non-steroidal anti-inflammatory agents, TNF-α inhibitors, interferon-α, leflunomide and a variety of chemotherapeutic agents, commonly used in the treatment of inflammatory illnesses such as methotrexate, azathioprine, chlorambucil and cyclophosphamide. The degree of splenic amyloid deposition was determined using Congo red staining of smears and a 5 grade scale. Results: The alkylating agents, chlorambucil and cyclophosphamide, each resulted in a significant 88% reduction in amyloid deposition, yielded the most striking effect on amyloidogenesis suppression in the enhanced mouse model (p < 0.0002). The non-steroidal anti-inflammatory agents tested varied widely in their ability to suppress amyloid formation in our mouse model, but only diflunisal was significantly effective, inducing a suppression of 57% (p = 0.04). Other chemotherapeutic agents tested, methotrexate and azathioprine, yielded 32% and 27% suppression, which fell short of statistical significance. Surprisingly, the immunomodulatory agents etanercept, infliximab, leflunomide and interferon-α had insignificant effects on amyloid formation in this model. Conclusion: Our findings suggest that alkylating agents may have a role in the prevention of amyloidogenesis. Further testing of these agents in animal models and in the clinical setting is needed.

Original languageEnglish
Pages (from-to)18-21
Number of pages4
JournalAutoimmunity Reviews
Volume12
Issue number1
DOIs
StatePublished - Nov 2012

Keywords

  • AA amyloidosis
  • Alkylating agents
  • Amyloidogenesis
  • Chlorambucil
  • Cyclophosphamide
  • Diclofenac
  • Diflunisal
  • NSAIDs
  • Serum amyloid A
  • TNF-α blockers

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