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.
Ogita
S
S
Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Japan.
Tsuto
T
T
Nakamura
K
K
Deguchi
E
E
Tokiwa
K
K
Iwai
N
N
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D015552:Injections, Intralesional; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D018191:Lymphangioma, Cystic / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010844:Picibanil / Q000008:administration & dosage*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D016207:Cytokines; D010844:Picibanil