Modulation of the antilisterial activity of human blood-derived macrophages by activating and deactivating cytokines

J Interferon Cytokine Res. 1995 Feb;15(2):105-14. doi: 10.1089/jir.1995.15.105.


A concept of macrophage deactivation by hormones and cytokines that opposes activation was recently proposed. Deactivation of the antilisterial activity of macrophages by IL-4, IL-10, and TGF-beta, as well as by dexamethasone, was studied here. IL-4, IL-10, and dexamethasone, but not TGF-beta, caused a complete loss of the competence of human blood-derived macrophages infected with Listeria monocytogenes to control or eliminate ingested bacteria. IL-10 and, to a lesser degree, dexamethasone lessened in parallel the capacity of macrophages to secrete H2O2. The antilisterial activity of cells simultaneously exposed to deactivating agents could be significantly augmented by IFN-gamma. Likewise, TNF-alpha and to a limited degree GM-CSF increased the antilisterial activity of cells treated with IL-10 and dexamethasone but not that of cells treated with IL-4. Suppression of TNF-alpha secretion in response to Listeria by TGF-beta, IL-10, dexamethasone, or pentoxifylline did not closely parallel antilisterial activity. Studies by transmission electron microscopy and actin staining suggested that deactivation by IL-10, IL-4, and dexamethasone of human blood-derived macrophages resulted in intraphagosomal multiplication of Listeria followed only then by an escape of bacteria into the cytoplasm. The antibacterial competence of human macrophages is lessened by IL-4 and IL-10 and augmented by IFN-gamma, TNF-alpha, and GM-CSF. The success of human macrophages in controlling intracellular pathogens appears to depend on the balance of activating and deactivating mediators modulating their activity.

Publication types

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

MeSH terms

  • Cytokines / immunology*
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Immunologic
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology
  • Interleukin-4 / pharmacology
  • Listeria / drug effects
  • Listeria / immunology*
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology*
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Macrophages / ultrastructure
  • Microscopy, Electron
  • Phagocytosis / immunology
  • Recombinant Proteins / pharmacology
  • Respiratory Burst / immunology
  • Transforming Growth Factor beta / pharmacology
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Dexamethasone
  • Interferon-gamma