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

• Published in: Journal of pediatric surgery 2003-12, Vol.38 (12), p.1806-1809
• Main Authors: Fujino, Akihiro, Moriya, Yoichiro, Morikawa, Yasuhide, Hoshino, Ken, Watanabe, Toshihiko, Shimojima, Naoki, Kitajima, Masaki
• Format: Article
• Language: English
• Subjects: Child, Preschool; Cytokines - analysis; cytotoxicity; Enzyme-Linked Immunosorbent Assay; Female; fibrotic change; Humans; Infant, Newborn; Injections; Lymphangioma; Lymphangioma, Cystic - drug therapy; Lymphangioma, Cystic - immunology; Male; OK-432; Picibanil - immunology; Picibanil - therapeutic use; transforming growth factor beta-1; vascular endothelial growth factor
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2003.08.041

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-β1), interleukin (IL)-6, IL-8, IL-12+p40, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) 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-β1 levels for a few weeks after the OK-432 injection. IL-6, IL-8, IL-12+p40, TNF-α, and IFN-γ 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.