Abstract

Abstract Leprosy is a still a serious human health problema in developed countries. Environmental and genetic factors are playing a key role in the chronic course of the disease, resistance versus susceptibility.  The multidrug treatment is not effective for all infected individuals; “cured” individuals mostly show relapses of neurological disordes and potential as the same as not cured can present physical and deformed constrainst.  The unsolved puzzle in leprosy is that clinic spectrum depends of the host immune response.and thus, the outcome of the immune response. In the present review we intended to describe some aspects of the immunotherapy, based on  type I IFNs and M. bovis BCG vaccine as a strategy such as sword to target germinal centers, either for the generation or for the enhancement and thus, throughout key signals delivered by folicular CD4+ T cells, and controlled by folicular regulatory CD4+ T cells, B cell differentiation into plasmacytoid cells be highly promoted the induction of protective high affinity neutralyzing antibodies to unlock  humoral immunity, protective toward M. leprae infected individuals.

Abstract The aim of this study is to evaluate the effects of corticosteroid application on each grade of burn, and to clarify the underlying mechanisms of the effects, especially in its acute inflammatory phase. To generate three-graded burn models (epidermal burn, or EB; dermal burn, or DB; and subcutaneous burn, or SB), hot water was applied on the back skin of Hos:HR-1 mice. Strongest-class (or high-potent) corticosteroid ointment (DD group) or petrolatum (control group) was applied on the back immediately after the hot water application on mice. Prednisolone sodium succinate (PDN group), 1 mg/kg was orally applied immediately after the hot water application on mice. The mice were sacrificed 1–3 days after hot water application, and the lesional skin samples were provided for histological assessment to enumerate the number of infiltrating inflammatory cells. The mRNA expression levels of inflammatory cytokines ( IL-1 b , TNF a , IL-6 and IFN g ) in the lesional skin were also investigated. As a result, corticosteroid application suppressed the number of infiltrating inflammatory cells in the DD group of EB and SB at the early phase, and in DB at all time-points. However, the number of infiltrating inflammatory cells increased in EB on day 3. Expression of cytokines was generally suppressed in the PDN group of SB. In the cases of EB and DB, some cytokines had decreased but many of the others showed increased expression. In conclusion, the anti-inflammatory effects of corticosteroids are not simple inhibitory effects on inflammatory cell infiltration and cytokine production, but exert more complicated effects in vivo .

Abstract Exercise-induced production of interleukin (IL)-6 results in the expression of chemokine CXC-motif ligand 1 (CXCL1) in mice. Recent studies described the increase in serum IL-6 levels during immersion of subjects in hot water. The present study investigated the effects of a 20-min head-out water immersion in 42 °C water (hot-HOI) on serum concentrations of CXCL1 in eight healthy men. Venous blood samples were taken at rest, immediately after hot-HOI, as well as 1, 2, 3, and 4 h after hot-HOI for measurements of serum concentrations of CXCL1, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hsCRP), while assessing counts of blood cells (CBC) and monitoring core temperature (Tcore). Tcore and serum IL-6 increased during hot-HOI and remained high until 4 h after hot-HOI. However, serum CXCL1, TNF-α, hsCRP, and CBC remained constant throughout the experiment. In conclusion, the results from our study demonstrated that 20-min hot-HOI increased serum IL-6, but not CXCL1 in healthy man.

Abstract Prompt elimination of pathogens including bacteria and dead cells prevents the expansion of secondary and prolonged inflammations and tissue damage. Keigairengyoto (KRT) is a traditional Japanese medicine prescribed for dermatoses such as purulent inflammations. Our aim is to clarify the actions of KRT in bacterial clearance and to examine the cell-kinetic profiles of phagocytes. In a mouse cutaneous infection model using living Staphylococcus aureus , KRT drastically reduced the number of bacteria in the infection sites. To evaluate the bacterial clearance, pseudo-infection was induced in mouse ears by intradermal injection of FITC-conjugated dead S. aureus . Biochemical and histological examinations revealed that KRT promoted bacterial clearance at 6 and 24 h post-injection. The numbers and phagocytic activities of neutrophils and macrophages in the ears were evaluated histologically using anti-Ly6G and F4/80 antibodies. KRT reduced bacterial deposition and increased the accumulation of F4/80 + resident macrophages around the lesion site. FACS analysis was performed on single cell suspensions dispersed enzymatically from skin lesions, followed by an investigation of CD11b + Ly6G + (neutrophils) and CD11b + Ly6G – (monocytes/macrophages) cells. KRT increased the mean fluorescent intensity of FITC in CD11b + Ly6G – cells and the number of FITC-positive CD11b + Ly6G + cells, while KRT did not change the numbers of these cells. To investigate the active constituents of KRT, phagocytosis assay using macrophages was performed, resulting in that some flavonoid glucuronides of KRT derivatives augmented phagocytosis. Collectively, KRT promoted bacterial clearance by enhancing the phagocytic capability of neutrophils and macrophages. KRT may exert unique properties in preventive and therapeutic strategies for skin infectious inflammation.

Abstract Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of "next-generation" sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

Abstract Obesity has become a significant public health problem since it may cause many chronic diseases, including type 2 diabetes, cardiovascular diseases, liver diseases, and some cancers. Recent studies have shown that obesity is a major risk factor for the development of inflammatory skin diseases, including eczema, atopic dermatitis, and psoriasis. Inflammatory cytokines produced from adipose tissue and activation of innate immunity are considered as important factors in obesity-induced inflammation. However, the molecular mechanisms by which obesity affects the development of inflammatory skin diseases are not well understood. In this review, we will discuss the relationship between the underlying mechanisms linking obesity and inflammatory skin diseases based on the latest researches.

Abstract Hailey-Hailey disease is an autosomal dominant hereditary skin disease. Severe cases are often difficult to treat. We report a recent case that was successfully treated using cyclosporine. The case is described from the aspects of treatment and gene mutation.