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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.

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.
AuthorsI Tsuchiya, T Kasahara, K Yamashita, Y C Ko, K Kanazawa, K Matsushima, N Mukaida
JournalCytokine (Cytokine) Vol. 5 Issue 6 Pg. 595-603 (Nov 1993) ISSN: 1043-4666 [Print] England
PMID8186372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chemotactic Factors
  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Picibanil
  • Complement C5a
Topics
  • Adult
  • Aged
  • Chemotactic Factors (biosynthesis, 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, pathology)
  • Picibanil (administration & dosage)
  • Pleural Effusion, Malignant (immunology, pathology)
  • Tumor Necrosis Factor-alpha (metabolism)

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