Balanced macrophage activation hypothesis: a biological model for development of drugs targeted at macrophage functional states

Pathobiology. 1999;67(5-6):277-81. doi: 10.1159/000028079.


Macrophages play a central role in the immune response and are major targets for chronic infection with viruses such as HIV. Recent studies on macrophage differentiation have shown the existence of classical activation and the counter-balancing anti-inflammatory alternative activation states. In the 'balanced macrophage activation hypothesis' we propose that macrophage activation is a cyclic process that balances these two states to achieve proper immunologic function. Dysregulation of this cycle would, therefore, be associated with various forms of chronic disease. This model has been utilized in the drug development of WF10, a novel macrophage-targeted drug, currently in advanced clinical testing for the treatment of HIV disease.

Publication types

  • Review

MeSH terms

  • Antigen Presentation / drug effects
  • Antigen Presentation / immunology
  • Chlorine / pharmacology
  • Humans
  • In Vitro Techniques
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Models, Biological
  • Oxides / pharmacology
  • Phagocytosis / drug effects
  • Th1 Cells / drug effects
  • Th2 Cells / drug effects


  • Oxides
  • Chlorine
  • tetrachlorodecaoxide