Subject(s)
Allergy and Immunology/history , Lymphatic Abnormalities/immunology , Lymphedema/immunology , History, 21st Century , Humans , Lymphatic Abnormalities/genetics , Lymphatic Abnormalities/pathology , Lymphedema/genetics , Lymphedema/pathology , Lymphoid Tissue/immunology , Lymphoid Tissue/pathology , WorkforceABSTRACT
PURPOSE: We have recently shown that the relative TLR4 expression on monocytes of low responding pediatric patients after OK-432 treatment is significantly reduced after stimulation with lipopolysaccharide (LPS) compared with high responding children. The aim of this study was to perform further analysis to explain this observation. METHODS: Monocytes from children with high (HR, n = 5) and low response (LR, n = 6) after previous OK-432 treatment were stimulated with LPS for 20 h and analyzed with fluorescence-activated cell sorting (mean fluorescence intensity, MFI; level of significance P ≤ 0.05). RESULTS: Mean MFI after LPS stimulation was comparable in both groups (HR 1142 ± 652 units, LR 839 ± 427 units, P = 0.85). Significant changes after LPS stimulation are explained by higher pre-stimulation values in the LR group compared with the HR group (950 ± 718 vs. 477 ± 341, P = 0.25) with considerable differences of the mean expression changes after LPS stimulation (HR 665 ± 683 vs. LR -111 ± 605, P = 0.08). CONCLUSION: The previously shown reduced TLR4 upregulation on monocytes after LPS stimulation in the LR group compared with the HR group can be primarily explained by TLR preconditioning. This observation implies the use of absolute values with definite thresholds.
Subject(s)
Lipopolysaccharides/immunology , Lymphatic Abnormalities/therapy , Monocytes/immunology , Picibanil/administration & dosage , Sclerosing Solutions/administration & dosage , Toll-Like Receptor 4/biosynthesis , Child , Child, Preschool , Female , Humans , Infant , Lymphatic Abnormalities/immunology , Male , Picibanil/immunology , Toll-Like Receptor 4/immunologyABSTRACT
Lymphatic vessels transport interstitial fluid, soluble Ag, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower Ab titers. In contrast, although delayed, T cell responses were robust after 21 d, including high levels of Ag-specific CD8+ T cells and production of IFN-γ, IL-4, and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. In addition, 1-y-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity.
Subject(s)
Dermis/immunology , Immune Tolerance/genetics , Immunity, Humoral/genetics , Lymphatic Abnormalities/immunology , Lymphatic Vessels/immunology , Vascular Endothelial Growth Factor Receptor-3/genetics , Animals , Autoantibodies/genetics , Cell Migration Inhibition/genetics , Cell Migration Inhibition/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dendritic Cells/pathology , Dermis/metabolism , Dermis/pathology , Drainage , Lymph Nodes/immunology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphatic Abnormalities/genetics , Lymphatic Abnormalities/pathology , Lymphatic Vessels/pathology , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1ß, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.