Corticosteroids (CSs) are used frequently in the neurocritical care unit mainly for their antiinflammatory and immunosuppressive effects. Despite their broad use, limited evidence exists for their efficacy in diseases confronted in the neurocritical care setting. There are considerable safety concerns associated with administering these drugs and should be limited to specific conditions in which their benefits outweigh the risks. The application of CSs in neurologic diseases, range from traumatic head and spinal cord injuries to central nervous system infections. Based on animal studies, it is speculated that the benefit of CSs therapy in brain and spinal cord, include neuroprotection from free radicals, specifically when given at a higher supraphysiologic doses. Regardless of these advantages and promising results in animal studies, clinical trials have failed to show a significant benefit of CSs administration on neurologic outcomes or mortality in patients with head and acute spinal injuries. This article reviews various chemical structures between natural and synthetic steroids, discuss its pharmacokinetic and pharmacodynamic profiles, and describe their use in clinical practice.

OBJECTIVEInflammation is an important factor in the development of insulin resistance, type 2 diabetes, and fatty liver disease. As a member of the tumor necrosis factor receptor superfamily (TNFRSF9) expressed on immune cells, 4-1BB/CD137 provides a bidirectional inflammatory signal through binding to its ligand 4-1BBL. Both 4-1BB and 4-1BBL have been shown to play an important role in the pathogenesis of various inflammatory diseases.RESEARCH DESIGN AND METHODSEight-week-old male 4-1BB–deficient and wild-type (WT) mice were fed a high-fat diet (HFD) or a regular diet for 9 weeks.RESULTSWe demonstrate that 4-1BB deficiency protects against HFD-induced obesity, glucose intolerance, and fatty liver disease. The 4-1BB–deficient mice fed an HFD showed less body weight gain, adiposity, adipose infiltration of macrophages/T cells, and tissue levels of inflammatory cytokines (e.g., TNF-α, interleukin-6, and monocyte chemoattractant protein-1 [MCP-1]) compared with HFD-fed control mice. HFD-induced glucose intolerance/insulin resistance and fatty liver were also markedly attenuated in the 4-1BB–deficient mice.CONCLUSIONSThese findings suggest that 4-1BB and 4-1BBL may be useful therapeutic targets for combating obesity-induced inflammation and metabolic disorders.