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Dengue virus (DV) infection is a major problem in public health. It can cause fatal diseases such as Dengue hemorrhagic fever and Dengue shock syndrome. Dendritic cells (DC) are professional APCs required for establishing a primary immune response. Here, we investigated the role of human PBMC-derived DC in DV infection. Using different techniques, including plaque assay, flow cytometry analysis, nested RT-PCR, and confocal microscope and electron microscope examinations, we show that DV can enter cultured human DC and produce virus particles. After entrance, DV could be visualized in cystic vesicles, vacuoles, and the endoplasmic reticulum. The DV-infected DC also showed proliferation and hypertrophy of the endoplasmic reticulum as well as the swollen mitochondria. In addition, the DV-stimulated DC could express maturation markers such as B7-1, B7-2, HLA-DR, CD11b, and CD83. Furthermore, the infection of DC by DV induced production of TNF-alpha and IFN-alpha, but not IL-6 and IL-12. Although DC underwent spontaneous apoptosis in the absence of feeding cytokines, this process appeared to be delayed after DV infection. Our observations provide important information in understanding the pathogenesis of DV infection.

Graft versus host disease (GVHD) remains the major obstacle to the widespread application of allogeneic bone marrow transplantation (BMT) despite improvement in drug prophylaxis. T cells in the donor bone marrow recognize and react against host alloantigens and thereby initiate GVHD, but the precise mechanisms by which host tissues are damaged remain unclear. In the current study, we determined the cytokine secretion, cell population distribution, and cell surface markers expression by ELISA and flow cytometer, to understand further the pathophysiology of GVHD. Our results demonstrated that there was no significant change in the cell ratio of B-and T- lymphocytes, and helper/suppressor cells during GVHD development when compared to the condition before transplantation. Furthermore, the percentage of natural killer cells, the interleukin-2 receptor (IL-2R) or the HLA-DR antigen on both CD4 and CD8 positive cells presented no significant difference between pre-transplantation and during GVHD. The serum cytokine secretion of IL-1, TNF-alpha, IL-2, ICAM-1, endothelin, TGF-beta showed no difference before BMT and during GVHD. However, when patients in the developing of GVHD, there was significant difference in the serum levels of soluble IL-2R (slL-2R), epidermal growth factor (EGF), and platelet derived growth factor (PDGF). In addition, with patients who develop GVHD, the mixed lymphocyte reaction also presented a significant difference. This study indicated that some serum cytokines such as sIL-2R, growth factors, and the mixed lymphocyte reaction may be used as parameters for the early detection of the development of GVHD.

Endomyocardial biopsy is generally used to quantify heart allograft rejection and guide immunotherapy. Biopsy, however, is invasive, costly, and risky. Since rejection requires lymphocyte activation, the purpose of this study was to assess alternative methods to evaluate rejection dynamics by investigating serum levels of cytokines and cell surface markers after heart transplantation. Interleukin-2-receptor bearing CD4+T (IL-2R/CD4) cell levels were higher in the peripheral blood of human transplant recipients with rejection grade 2 (p < 0.02). HLA-DR/CD3 levels were somewhat higher in rejection grade 2. There was no correlation between biopsy scores and serum levels of tumor necrosis factor (TNF-alpha), IL-2, or percentage of T cell, NK cell, B cell, CD4+T cell, CD8+T cell, HLA-DR/CD4, HLA-DR/CD8, IL-2R/CD3, IL-2R/CD8. Interleukin-1 (IL-1 beta) was not detectable in all of the samples. The current studies suggest that monitoring lymphocyte IL-2R/CD4 and HLA-DR/CD3 levels is useful in predicting cardiac transplant rejection.

Heat stroke is a disease characterized by high fever. Cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-delta) play a major role in fever production. In the current studies, eight patients with heat stroke were enrolled in a cytokine studies. Serum cytokine levels of these patients were determined by EIA methods, and in vitro IL-1 and IL-1 inhibitor production were determined by murine thymocyte proliferation assay and/or EIA. Significantly high levels of circulating IL-1, TNF-delta, and IL-6 were demonstrated. Positive correlations were demonstrated between the body temperature and the level of IL-1 beta, and the cooling time and level of serum IL-1 beta. In addition, monocytes from heat stroke patients after complete recovery, secreted a much higher amount of IL-1 than did normal volunteers. However, there was no difference in IL-1 inhibitor production. These results indicate that cytokines may play a major role in the pathogenesis of heat stroke, and the ability to make different amounts of IL-1 in response to exogenous stimulation appear to be risk factors for an attack of heat stroke.

To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were analyzed in fresh blood T cells from 20 SLE patients who had not yet received any treatment. Th1 and Th2 cells were quantitated based on their intracellular cytokine content as assessed by flow cytometry. Cytokine expressions were correlated with clinical features, laboratory findings, and disease activities. There was no difference in the expression of intracellular IFN-γ, or IL-4 between SLE patients and healthy controls. However, the IL-2 and IL-10 levels were significantly higher and lower respectively in the lupus patients than in the control group. In addition, patients with arthritis had higher IFN-γ expression than patients without arthritis. Moreover, patients with serositis or CNS involvement had higher IL-4 expression than in patients without these manifestations. There was no correlation between the SLEDAI scores and the cytokine expression levels. However, patients with serum anti-ds DNA antibodies had higher IL-10 levels than in those without these antibodies. The present study demonstrates that a Th1 pattern of intracellular cytokines predominates in patients with SLE prior to treatment. The pattern of particular intracellular T cell cytokines may suggest specific clinical manifestations and disease progression of SLE. [ABSTRACT FROM AUTHOR]