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.
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.
Tsuchiya
I
I
Department of Surgery, Jichi Medical School, Tochigi-ken, Japan.
Kasahara
T
T
Yamashita
K
K
Ko
Y C
YC
Kanazawa
K
K
Matsushima
K
K
Mukaida
N
N
D000328:Adult; D000368:Aged; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000302:isolation & purification; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002847:Chromatography, Agarose; D015936:Complement C5a / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010844:Picibanil / Q000008:administration & dosage*; D016066:Pleural Effusion, Malignant / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D015936:Complement C5a