CRL-1072 enhances antimycobacterial activity of human macrophages through interleukin-8. Academic Article uri icon

Overview

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-alpha (TNF-alpha), 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.

publication date

  • January 1, 1999

Research

keywords

  • Interleukin-8
  • Macrophages
  • Mycobacterium avium
  • Poloxamer
  • Surface-Active Agents

Identity

Scopus Document Identifier

  • 0032938646

Digital Object Identifier (DOI)

  • 10.1089/107999099314432

PubMed ID

  • 10048770

Additional Document Info

volume

  • 19

issue

  • 1