Could GILZ Be the Answer to Glucocorticoid Toxicity in Lupus?
Abstract
Glucocorticoids (GC) are used globally to treat autoimmune and inflammatory disorders. Their anti-inflammatory actions are mainly mediated via binding to the glucocorticoid receptor (GR), creating a GC/GR complex, which acts in both the cytoplasm and nucleus to regulate the transcription of a host of target genes. As a result, signaling pathways such as NF-κB and AP-1 are inhibited, and cell activation, differentiation and survival and cytokine and chemokine production are suppressed. However, the gene regulation by GC can also cause severe side effects in patients. Systemic lupus erythematosus (SLE or lupus) is a multisystem autoimmune disease, characterized by a poorly regulated immune response leading to chronic inflammation and dysfunction of multiple organs, for which GC is the major current therapy. Long-term GC use, however, can cause debilitating adverse consequences for patients including diabetes, cardiovascular disease and osteoporosis and contributes to irreversible organ damage. To date, there is no alternative treatment which can replicate the rapid effects of GC across multiple immune cell functions, effecting disease control during disease flares. Research efforts have focused on finding alternatives to GC, whic...Continue Reading
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