A role of cytokines in OK-432 injection therapy for cystic lymphangioma: an approach to the mechanism

Abstract

Purpose: This study examines cytokine levels of aspirates from cystic lymphangiomas after injection of OK-432 and over the course of several weeks to better understand the process of tumor regression.

Methods: Fluids aspirated from lymphangioma cysts of 3 patients were collected sequentially before and after OK-432 injection. Mononuclear cells (MNCs) were separated and cultured with or without OK-432. Vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR1), sVEGFR2, transforming growth factor beta-1 (TGF-beta1), interleukin (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) levels in the supernatants of the aspirates and the culture supernatants of MNCs were then measured by ELISA.

Results: The aspirates exhibited a marked elevation in IL-6, IL-8, VEGF, and TGF-beta1 levels for a few weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-alpha, and IFN-gamma levels were elevated in the culture supernatants of the MNC cultured with OK-432 for up to 9 days. All the tumors regressed significantly, with sclerotic change, within 3 months after OK-432 injection.

Conclusions: Cytokine production is maintained for a few weeks after OK-432 injection. Fibrotic changes may be another main mechanism in tumor regression in addition to cytotoxic effects on lymphangioma cells. A close relationship between cytokines from intracystic cells and lymphangioma cells is suggested.