Alternative activation of macrophages

Nat Rev Immunol. 2003 Jan;3(1):23-35. doi: 10.1038/nri978.


The classical pathway of interferon-gamma-dependent activation of macrophages by T helper 1 (T(H)1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Cell Differentiation / immunology
  • Chemokines / immunology
  • Humans
  • Interleukin-13 / immunology*
  • Interleukin-4 / immunology*
  • Macrophage Activation / immunology*
  • Mice
  • Th2 Cells / immunology


  • Chemokines
  • Interleukin-13
  • Interleukin-4