OK-432 therapy for lymphangioma in children: why and how does it work?

Intralesional injection of OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) is safe and effective therapy for lymphangioma. The authors evaluated the mechanism of this therapy in 6 patients who had cystic lymphangioma. The intracystic fluid of the cystic lymphangioma was aspirated before and after (on days 1 and 4) the OK-432 therapy. Changes in cell populations and cytokine productions in each aspirated fluid were analyzed. White blood cells in the intracystic fluid increased markedly in number. Before OK-432 therapy, 96% of the intracystic white blood cells were lymphocytes, and the remaining were neutrophils and macrophages. On day 1, the percentages of neutrophils and macrophages increased to 72% and 21%, respectively. On day 4, the percentage of lymphocytes increased to 72%. Flow cytometry analysis using monoclonal antibodies showed that the number of natural killer cells (CD56+) and T cells (CD3+) had increased. The activity of cytotoxic tumor necrosis factor (TNF) and interleukin-6 increased immediately after OK-432 injection and remained high in titer until day 4. These findings suggest that the white blood cells induced and activated by OK-432, and the cytokines (including TNF) produced by these cells increased the endothelial permeability, and thus the accelerated lymph drainage and increased lymph flow let to shrinkage of the cystic spaces.