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The Role of Glucocorticoids in Inflammatory Diseases.

ABSTRACT: For more than 70 years, glucocorticoids (GCs) have been a powerful and affordable treatment option for inflammatory diseases. However, their benefits do not come without a cost, since GCs also cause side effects. Therefore, strong efforts are being made to improve their therapeutic index. In this review, we illustrate the mechanisms and target cells of GCs in the pathogenesis and treatment of some of the most frequent inflammatory disorders affecting the central nervous system, the gastrointestinal tract, the lung, and the joints, as well as graft-versus-host disease, which often develops after hematopoietic stem cell transplantation. In addition, an overview is provided of novel approaches aimed at improving GC therapy based on chemical modifications or GC delivery using nanoformulations. GCs remain a topic of highly active scientific research despite being one of the oldest class of drugs in medical use.

SUBMITTER: Reichardt SD

PROVIDER: S-EPMC8616489 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood. Comparing peripheral blood from patients with sarcoidosis to controls, 872 transcripts were upregulated and 1039 were downregulated at >1.5-fold change and a significant q value. Several transcripts associated with interferon and STAT1 were upregulated. Lung and lymph node analyses also showed dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas in lymph nodes of patients with sarcoidosis expressed abundant STAT1 and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis. This novel hypothesis unites seemingly disparate observations with regard to sarcoidosis including implication of a casual role for interferons, a suspected infectious trigger, TH1 predominating lymphocytes in bronchoalveolar lavage, and the association with hypercalcemia. This study tested the hypothesis that SpA is characterized by a distinct pattern of gene expression in peripheral blood of affected individuals compared with healthy controls. High-density, human GeneChip probe arrays were used to profile mRNA of peripheral blood cells from 18 subjects with SpA and 25 normal individuals. Samples were processed as two separate sets at different times. Blood samples were taken at a time when patients were not receiving systemic immunomodulatory therapy. Differential expression was defined as a 1.5-fold change with a q value <5%. Gene ontology and pathway information were also studied. Signals from 134 probe sets (representing 95 known and 12 unknown gene transcripts) were consistently different from controls in both Sets 1 and 2. Included among these were transcripts for a group of 20 genes, such as interleukin-1 receptors 1 and 2, NLRP2, SLPI, SPARC, and TREM-1 that are clearly related to the immune or inflammatory response and a group of 4 transcripts that have a strong role in bone remodeling. Our observations are the first to implicate SPARC, SLPI, and NLRP2, a component of the innate immune system, in the pathogenesis of SpA. Our results also indicate a possible role for interleukin-1 and its receptors in SpA. In accord with the bone pathology component of SpA, we also found that expression levels of transcripts reflecting bone remodeling factors are also distinguishable in peripheral blood from patients with SpA versus controls. These results confirm some previously identified biomarkers implicated in the pathogenesis of SpA and also point to novel mediators in this disease. Peripheral blood was collected from diseased and control subjects. The sarcoidosis portion of the study included 12 patients and 12 control subjects. The spondyloarthropathy study was done in two independent sets. The first set included 11 patients and the same 12 control subjects used for the sarcoidosis study. The second set included 7 patients and 13 control subjects. For each sample, total RNA was isolated and analyzed by hybridization on Affymetrix arrays.

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The Role of Glucocorticoids in Inflammatory Diseases.

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