CRL-1072 enhances antimycobacterial activity of human macrophages through interleukin-8

Chinnaswamy Jagannath, Suresh Pai, Jeffrey K. Actor, Robert L. Hunter

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

CRL-1072 is a poloxamer surfactant that kills mycobacteria more effectively within macrophages than in broth cultures. Human macrophages treated with CRL-1072 synthesized interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM- CSF) in a dose-dependent manner. About 3000 pg of IL-8 per million human macrophages accumulated in cultures treated with 100-1500 ng of poloxamer, with mRNA message for IL-8 induced as early as 2 h. As macrophages do not have IL-RA receptors, a transwell culture was used to study the chemotactic and activating effects of IL-8 between CRL-1072-treated human macrophage effectors and polymorphonuclear neutrophil (PMN) targets. PMN were activated by IL-8 and secreted hydrogen peroxide and myeloperoxidase (MPO). MPO derived from PMN, in turn, activated monocytes for an enhanced killing of intracellular Mycobacterium avium. The ability of CRL-1072 to modulate macrophage-mediated activation of neutrophils and receive a feedback activation signal may form one mechanism by which its antimycobacterial activity is achieved in vivo.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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