Disease exacerbation by etanercept in a mouse model of alphaviral arthritis and myositis

Arthritis Rheum. 2011 Feb;63(2):488-91. doi: 10.1002/art.30112.

Abstract

Objective: Mosquito-borne alphaviruses such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV) cause sporadic, sometimes large, outbreaks of rheumatic disease worldwide. This study was designed to test the effect of treating RRV-induced arthritis using the anti-tumor necrosis factor (anti-TNF) drug etanercept in a mouse model of rheumatic disease.

Methods: Mice were infected with RRV and treated with etanercept. Weight gain was measured, tissue viral titers were determined, and histologic changes in muscle and joint tissues were assessed.

Results: RRV-infected mice treated with etanercept showed decreased weight gain, higher viral titers in muscle, joints, and blood, and more tissue damage and inflammatory cell recruitment than RRV-infected mice without treatment.

Conclusion: Anti-TNF therapy is unlikely to be useful in treating alphaviral arthritides. During alphaviral epidemics, careful monitoring of patients being treated with anti-TNF agents may be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus / immunology
  • Alphavirus Infections / complications
  • Alphavirus Infections / drug therapy*
  • Alphavirus Infections / pathology
  • Animals
  • Ankle Joint / drug effects
  • Ankle Joint / pathology
  • Ankle Joint / virology
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / virology
  • Disease Models, Animal
  • Etanercept
  • Host-Pathogen Interactions / immunology
  • Immunoglobulin G / toxicity*
  • Immunosuppressive Agents / toxicity*
  • Longevity / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / virology
  • Myositis / drug therapy*
  • Myositis / pathology
  • Myositis / virology
  • Receptors, Tumor Necrosis Factor
  • Treatment Outcome
  • Viral Load
  • Weight Gain / drug effects

Substances

  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Etanercept