Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells.

BACKGROUND: Plasticity of CD4(+) lymphocyte Th17/regulatory T cell (Treg) subsets is involved in the pathogenesis of chronic airway inflammatory diseases, such as asthma. Reversal of Th17/Treg cell balance towards Treg cells may be beneficial for the suppression of chronic Th2 cell-mediated inflammatory diseases, such as asthma. However, the effect of the combination of corticosteroids and a statin on the ratio of Treg/Th17 cells is unknown. OBJECTIVE: We investigated the in vitro effects of the combination of simvastatin and fluticasone propionate (FP) on the numbers of Treg and Th17 cells in asthmatic patients after co-incubation with monocyte-derived DCs (mDCs), and explored the underlying signalling pathways involved. METHODS: Using flow cytometry, we determined the effects of FP and simvastatin on Treg/Th17 balance after co-incubation of asthmatic CD4(+) T cells with mDCs. We also measured the relevant Treg and Th17-polarizing cytokines released from mDCs and also investigated the role of indoleamine 2, 3-dioxygenase (IDO) in this response. RESULTS: The combination of simvastatin and FP significantly increased Treg and concomitantly reduced Th17 cell numbers to a greater extent than FP or statin treatment alone. The enhancing effects of simvastatin on FP effects were mediated through the up-regulation of indoleamine 2, 3-dioxygenase and interleukin (IL)-10, together with down-regulation of IL-6 and IL-23 expression in mDCs. CONCLUSION: On the basis of this in vitro model of asthma, we suggest that the combination of a statin and a corticosteroid could augment the Treg/Th17 cell ratio and thus more effectively suppress airway inflammation in asthma patients. This may be particularly relevant in the treatment of severe asthma where Th17 cells are activated and linked to neutrophilic inflammation.

Reference spirometric values for healthy lifetime nonsmokers in Thailand.

The normal spirometric reference values for Thai people are still not yet available. The aim of this study was to establish standard spirometric equations for Thai people. Subjects 10 years of age and over were selected and their demographic distributions represented that of the population of the whole country. Inclusion criteria were strictly lifetime nonsmokers, no history of chronic cardiopulmonary disease (using a modified ATS--DLD 78 respiratory adult questionnaire), normal standard chest radiograph and unremarkable physical examination. They had to be without respiratory symptoms at the time of the study. Spirometric values were obtained by 5 turbine system 'Pony graphic' (Cosmed, Italy) spirometers which met ATS recommendations. A normal group of 2299 women and 1655 men were selected. Regression analyses using sex, height and age as independent variables were used to provide equations for predicted values. The results were: [table: see text] FVC and FEV1 from this study are close to the Chinese but are 8-20 per cent lower than the Caucasians. These predicted equations are recommended to be used for future reference values in the Thai population.

An exotic pulmonary infection in Thailand: melioidosis.

Melioidosis is an infectious disease from Burkholderia pseudomallei and is confined in specific geographic areas such as Southeast Asia. Its highest prevalence in Thailand is in the north-eastern part. Most infected patients had worked paddy fields or had underlying diseases such as diabetes mellitus. Melioidosis can manifest clinically, with either disseminated or localized features. In the disseminated form patients developed an acute and progressive course with septicaemia. In contrast, patients with the localized form usually presented with prolonged fever, and symptoms of one or more organ involvement, in particular the lung and the liver. Definite diagnosis of melioidosis is made by an isolation of Burkholderia pseudomallei from a variety of clinical specimens. Treatment of choice for the septicaemic patients is an initial combination of ceftrazidime and trimethoprime-sulfamethoxazole, followed by trimethoprime-sulfamethoxazole for up to 6-12 months depending on the result of clinical specimen culture. Treatment for the localized form requires simultaneous antibiotic therapy and surgical drainage. However, optimum duration of antibiotic therapy remains unknown so further research is required. Melioidosis is an important disease in terms of mortality rate and it requires rapid diagnosis and treatment. To prevent recurrence, it is necessary to continue oral doxycycline or trimethoprime-sulfamethoxazole for 6-12 months.