Neutrophil chemotactic factors induced by OK-432 in the treatment of malignant pleural effusion

To investigate the mechanism of neutrophil migration into the pleural effusion in patients undergoing intrapleural immunotherapy with the streptococal agent OK-432 for malignant pleurisy, we examined the levels of neutrophil chemotactic factor in the pleural fluid. Pleural fluid was collected before and after instillation of OK-432 in 19 patients with lung cancer, one with breast cancer, and one with gastric cancer. First we evaluated the neutrophil chemotactic activity measured by Byoden's method and the change of the cellular compositition of pleural fluid. Neutrophil chemotactic activity was significantly increased 6 hours after the instillation of OK-432, as were the differential neutrophil count and the absolute number of neutrophils. Moreover, there was a close correlation between the absolute neutrophil count and the neutrophil chemotactic activity. We also measured the levels of complement compo-nent C5a and interleukin-8 (IL-8), which are thought to be neutrophil chemotactic factor, before and after intrapleural injection of OK-432. The IL-8 and C5a levels were significantly elevated after OK-432 injection. The change of the IL-8 level was associated with a marked increase both in the neutrophil chemotactic activity and in the neutrophil absolute count. In addition, we evaluated the cytokine levels (IL-1β, IL-6 and soluble interleukin-2 receptor) of pleural fluid before and after OK-432 treatment. The OK-432 treatment induced a marked increase in the levels of IL-1β and IL-6. However, the pleural fluid level of sIL-2R was not significantly elevated, although it was significantly higher than the serum level. These findings suggest that OK-432 intrapleural injection induces neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1β and Il-6), which attracts neutrophils into the pleural space, which may be involved in the mechanism of the sclerosing effect of OK-432.

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