A Role of Cytokines in OK-432 Injection Therapy for Cystic Lymphangioma: An Approach to the Mechanism

Akihiro Fujino, Yoichiro Moriya, Yasuhide Morikawa, Ken Hoshino, Toshihiko Watanabe, Naoki Shimojima, Masaki Kitajima

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1806-1809
Number of pages4
JournalJournal of Pediatric Surgery
Issue number12
Publication statusPublished - 2003 Dec
Externally publishedYes


  • Cytotoxicity
  • Fibrotic change
  • Lymphangioma
  • OK-432
  • Transforming growth factor beta-1
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health


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