Trehalose dimycolate (TDM) isolated from Nocardia asteroides induced in mice a severely wasted condition known as cachexia. Intraperitoneal injection of mice with five 10 micrograms doses of TDM in mineral oil at intervals of 2 d killed 90% of the animals within 26 d. Death followed a precipitous weight loss and an inflammatory process in the peritoneal cavity. When mice were injected intraperitoneally with a single 10 micrograms dose of TDM, 48 h later, they had begun to lose weight and exhibited extreme hypertriglyceridaemia and hypoglycaemia. Tumour necrosis factor (or cachectin) was detected in the plasma from animals injected with TDM. This cytokine released by mononuclear phagocytes may be involved in the induction of cachexia by TDM.

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How the immune system kills Mycobacterium tuberculosis is still a puzzle. The classical picture of killing due to phagocytosis by activated macrophages may be only partly correct. Based on recent evidence, we express here the view that cytotoxic T lymphocytes also make an important contribution and suggest that DNA vaccines might be a good way to enhance this.

Clinical data point to adverse cardiovascular events elicited by testosterone replacement therapy. Testosterone is the main hormone used in gender-affirming hormone therapy (GAHT) by transmasculine people. However, the cardiovascular impact of testosterone in experimental models of GAHT remains unknown. Sex hormones modulate T cells activation, and immune mechanisms contribute to cardiovascular risk. The present study evaluated whether testosterone negatively impacts female cardiovascular function by enhancing Th17 cells-linked effector mechanisms. Female (8 weeks-old) C57BL/6J mice received testosterone (48 mg.Kg-1.week-1) for 8 weeks. Male mice were used for phenotypical comparisons. The hormone-treatment in female mice increased circulating testosterone to levels observed in male mice. Testosterone increased lean body mass and body mass index, and decreased perigonadal fat mass, mimicking clinical findings. After 8 weeks, testosterone decreased endothelium-dependent vasodilation and increased circulating Th17 cells. After 24 weeks, testosterone increased blood pressure in female mice. Ovariectomy did not intensify phenotypical or cardiovascular effects by testosterone. Female mice lacking T and B cells [Rag1 knockout (-/-)], as well as female mice lacking IL-17 receptor (IL-17Ra-/-), did not exhibit vascular dysfunction induced by testosterone. Testosterone impaired endothelium-dependent vasodilation in female mice lacking γδ T cells, similarly to the observed in wild type female mice. Adoptive transfer of CD4+ T cells restored testosterone-induced vascular dysfunction in Rag1-/- female mice. Together, these data suggest that CD4+ T cells, most likely Th17 cells, are central to vascular dysfunction induced by testosterone in female mice, indicating that changes in immune cells balance are important in the GAHT in transmasculine people.

Steroidal hormones profiles can be used to distinguish different biological conditions by the amount of entities present especially in the context of disease. Knowing the levels of such molecules can be crucial to determining a biological response and/or unveil important phenomena. The emergence of high‐resolution methods has amplified the potential of MS and it is currently possible to identify numerous steroid species. In addition, sensitive and very specific modes of acquisition, such as high‐resolution multiple reaction monitoring (MRM), have contributed to this end. In this perspective special feature article, Lúcia Helena Faccioli and colleagues propose a high‐resolution MRM method to quantify steroidal hormones and their metabolites. The results indicate that the method can be applied for quantification of steroids in several biological samples, such as human plasma. Dr. Faccioli is Professor of immunology in the Dept. of Clinical Analyses, Toxicology and Bromatology at the University of Sao Paulo (Brazil). Her main research interests are centered on the study of inflammatory response and role of lipid mediators in several disease including tuberculosis. She also investigates natural products with anti‐inflammatory properties.

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