Plasmacytoid dendritic cells and interferon levels are increased in lymphatic malformations.

OBJECTIVE: Describe the presence of plasmacytoid dendritic cells and type 1 interferon and the activation of interferon signaling pathway in lymphatic malformations. DESIGN: Retrospective case series. MATERIALS: Nineteen lymphatic malformations with matching clinical data were compared to control tissue (normal skin and lymph node). METHODS: Paraffin-embedded tissue was evaluated for plasmacytoid dendritic cells, type 1 interferon, and type 1 interferon signaling with immunohistochemistry and RNA in situ hybridization. Staining results were compared with controls and correlated with clinical data with descriptive statistics and Mann-Whitney tests. RESULTS: Lymphatic malformations had increased staining for plasmacytoid dendritic cells, interferons alpha and beta, and phosphorylated signal transducer and activator of transcription 1 compared with controls (P < 0.05). Significantly increased interferon beta staining was present in recurrent lymphatic malformation tissue compared with nonrecurrent lymphatic malformations. CONCLUSION: Lymphatic malformations have unusual ongoing local immune activation, possibly affecting recurrence.

Analysis of cytokine levels in human lymphangiomas.

BACKGROUND: Different theories concerning the origin of lymphangiomas have been formulated but their precise pathogenesis is still unknown. This study aimed to analyze the levels of different cytokines in lymphangioma cyst fluids. MATERIALS AND METHODS: Fluid aspirates from lymphangioma cysts of five patients were obtained. The intracystic levels of interleukin (IL)-6, IL-8, IL-2R and tumor necrosis factor alpha (TNFalpha) were determined in four cases before and one case after OK-432 administration using an immunometric assay. RESULTS: Increased IL-6 levels were observed in all cases. Moreover, elevated IL-2R and TNFalpha levels were observed in three out of four and elevated IL-8 levels in two out of four untreated cases. There was a 25-fold increase in IL-6 after repeated OK-432 injections while IL-8, IL-2R and TNFalpha levels did not change significantly. CONCLUSION: These findings suggest that cytokines may be involved in the pathogenesis of lymphangiomas.

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

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.

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.

[The factors promoting dystrophic pathology of the hand and duodenal peptic ulcer in women]. / O faktorakh, sposobstvuiushchikh distroficheskoi patologii kisti i iazvennoi bolezni dvenadtsatiperstnoi kishki u zhenshchin.

The authors have made an attempt to make exact the reasons of the frequent association of hand dystrophic pathology and duodenal ulceration disease in women. It is revealed that pointed diseases are to be the late symptoms of equally directed alterations in the organism, including neuro-humoral and immune mechanisms of adaptation, occurring in women even in sexual maturing period and being the favourable background for occurrence of various diseases including hand dystrophic pathology and duodenal ulcerative disease.