How does prednisone work
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How Prednisone Works: Mechanisms and Effects
Anti-Inflammatory and Immunosuppressive Properties
Prednisone is a synthetic glucocorticoid widely used for its potent anti-inflammatory and immunosuppressive properties. It achieves these effects primarily by modulating the immune response and reducing inflammation. Prednisone inhibits the appearance of inflammatory mediators such as histamine and leukotriene C4 (LTC4) and blocks the influx of eosinophils and basophils, which are key players in allergic reactions and inflammation 15. This selective blockade of inflammatory cells and mediators contributes significantly to its effectiveness in treating conditions like asthma and allergic reactions 15.
Impact on Glucose Metabolism and Muscle Protein
While prednisone is effective in reducing inflammation, it also has notable side effects, particularly concerning glucose metabolism and muscle protein dynamics. Short-term use of prednisone has been shown to antagonize insulin's anabolic effects on muscle protein and glucose metabolism, leading to muscle insulin resistance and a blunted protein anabolic response . This interaction can result in muscle atrophy with prolonged use . Additionally, prednisone can cause significant increases in glycemic excursions and insulin levels, indicating impaired glucose tolerance .
Effects on Bone Turnover
Prednisone also affects bone metabolism. It has been observed to decrease markers of bone formation such as osteocalcin and procollagen peptides within hours of administration . This reduction in bone formation markers suggests that prednisone can negatively impact bone health, potentially leading to conditions like osteoporosis with long-term use .
Modulation of T Cell Function
In the context of cancer immunotherapy, prednisone has been studied for its effects on T cell function. Unlike dexamethasone, prednisone does not significantly compromise T cell cytokine production or proliferation when used in conjunction with immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 antibodies . This indicates that prednisone can be used to manage immune-related adverse events without severely impacting the efficacy of immunotherapy .
Gut Microbiota and Metabolites
Long-term prednisone treatment has been shown to alter the composition of the gut microbiota and fecal metabolites. Studies in rats have demonstrated changes in the relative abundance of specific gut bacteria and fungi, as well as alterations in fecal metabolites associated with metabolic pathways like phenylalanine and butanoate metabolism 68. These changes in the gut microbiome may contribute to some of the adverse effects associated with prolonged prednisone use 68.
Clinical Applications and Considerations
Prednisone is commonly used in the management of chronic conditions such as rheumatoid arthritis, where it helps alleviate symptoms and inhibit disease progression when used in low doses . Modified-release formulations of prednisone have been developed to counter the circadian rise in pro-inflammatory cytokines, improving patient outcomes by reducing morning stiffness and other symptoms .
Conclusion
Prednisone is a powerful glucocorticoid with significant anti-inflammatory and immunosuppressive effects. However, its use is accompanied by various side effects, including impaired glucose metabolism, muscle atrophy, and altered bone turnover. Understanding these mechanisms and effects is crucial for optimizing its therapeutic use while minimizing adverse outcomes.
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