Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, OK-432: role of IL-8 for neutrophil infiltration

Cytokine. 1993 Nov;5(6):595-603. doi: 10.1016/s1043-4666(05)80010-9.

Abstract

When OK-432, a well-known streptococcal preparation for an anti-tumour drug, was administered into the pleural cavity of patients with malignant pleurisy, a rapid and prominent leukocytosis, predominantly consisting of neutrophils, was observed in the cavity. Neutrophil infiltration usually peaked 6-9 h after OK-432 administration, and levelled down after 24 h. Prior to the neutrophil accumulation, transient but marked elevation of various inflammatory cytokine levels including IL-1 beta, TNF-alpha, IL-8 and G-CSF was observed. In particular, IL-8 levels increased more than 10-fold, while GM-CSF did not change significantly. A good correlation between IL-8 levels and neutrophil chemotactic response was observed particularly during 0-3 h. Specific neutralization or removal of IL-8 by antibody column abrogated half of the neutrophil chemotaxis, while neutralization of C5a removed around 40%. Sequential removal of IL-8 and C5a abrogated totally 80% of chemotaxis, confirming that these two factors are mostly responsible for the neutrophil chemotaxis in the pleural fluids. These results have suggested that rapid neutrophil infiltration induced by OK-432 in vivo is ascribable largely to IL-8 and in part to C5a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chemotactic Factors / biosynthesis
  • Chemotactic Factors / isolation & purification
  • Chemotaxis, Leukocyte / immunology
  • Chromatography, Agarose
  • Complement C5a / metabolism
  • Cytokines / biosynthesis*
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-8 / metabolism*
  • Male
  • Middle Aged
  • Neutralization Tests
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Picibanil / administration & dosage*
  • Pleural Effusion, Malignant / immunology*
  • Pleural Effusion, Malignant / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemotactic Factors
  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Picibanil
  • Complement C5a