Washington Anesthesia Partners

Uses of Dexamethasone

Dexamethasone is a potent corticosteroid used in the treatment of aggressive inflammation. Inflammation is present in many serious diseases, including cancers, autoimmune disorders, and infections. When inflammation is successfully treated, patients can experience marked improvement in prognosis and quality of life. Dexamethasone has many clinical uses, ranging from the treatment of asthma and severe allergies to reducing nausea and vomiting after anesthesia, and more.

Many studies have demonstrated that dexamethasone restores the integrity of epithelial barriers in different organs and tissues in instances of severe inflammation. While the mechanism of action is still being clarified, preliminary evidence shows that dexamethasone alters the immune cells in epithelial barriers to prevent entry of harmful substances that would compromise tissues or organs. This effect might underpin the variety of clinical uses of dexamethasone, as the drug mediates ‘cell talk’ between immune cells and the growth factors that stimulate the over-proliferation and migration in airway epithelia in chronic respiratory diseases like asthma.

A study by Grohmann et al. explores dexamethasone’s mode of action through the activation of a critical immunoregulatory pathway – the enzyme indoleamine 2,3-dioxygenase (IDO) activates the glucocorticoid-induced tumor necrosis factor receptor (GITR) in CD4+ T cells and GITRL in plasmacytoid dendritic cells (pDCs). This activation via reverse signaling through GITRL leverages the noncanonical NF-κB-dependent pathway, leading to enhanced tryptophan catabolism—a process crucial for mitigating inflammatory responses in allergic airway inflammation models such as asthma. This pathway prevents excessive airway hyperresponsiveness and inflammation. Other research by Rahmawati et al. suggests that dexamethasone effectively mitigates IL-17A-induced epithelial barrier disruption which is a critical factor in asthma pathology. By targeting the compromised barrier function, inflammation and airway hyperresponsiveness is reduced. 1,2,3

Dexamethasone’s potent anti-inflammatory qualities, along with its anti-nausea and pain-relieving capacities, underscore its widespread use in oncological care. Inflammation is common in cancer patients, presenting as a symptom as well as a side effect of radiation therapy. Chronic inflammation contributes to cancer development and progression; therefore regulating inflammatory pathways improves patient prognosis.5 Dexamethasone acts on pathways like NF-kB and JAK-STAT to mediate acute and chronic inflammatory responses. For example, a study by Saito et al. showed that dexamethasone reduced oral mucositis (OM) in breast cancer patients receiving chemotherapy. Their findings demonstrated that high doses of systemic dexamethasone significantly lowered the incidence of all-grade OM from 53.5% to 27.3% during the first cycle to combat inflammation. This reduction is crucial as OM not only diminishes quality of life through pain and discomfort but also compromises nutritional intake and increases risks for systemic infections due to compromised mucosal barriers. Dexamethasone not only suppresses pro-inflammatory cytokines such as IL-6 and TNF-α but also influences the recruitment and activation of immune cells within the tumor milieu.

However, this broad-spectrum anti-inflammatory action can be a double-edged sword. Long-term use of dexamethasone is associated with side effects such as metabolic dysregulation and increased susceptibility to infections due to its immunosuppressive properties. As such, careful patient monitoring is needed in each of dexamethasone’s many clinical uses.4,5

References

  1. Grohmann, Ursula, et al. “Reverse Signaling through GITR Ligand Enables Dexamethasone to Activate IDO in Allergy.” *Nature Medicine*, vol. 13, no. 5, May 2007, pp. 579-586. doi:10.1038/nm1563.
  2. Rahmawati, Siti Farah, et al. “Function-specific IL-17A and Dexamethasone Interactions in Primary Human Airway Epithelial Cells.” *Scientific Reports*, vol. 12, no. 1, 2022, https://doi.org/10.1038/s41598-022-15393-2.
  3. Choi, M., et al. “A New Combination Therapy for Asthma Using Dual-Function Dexamethasone-Conjugated Polyethylenimine and Vitamin D Binding Protein siRNA.” *Gene Therapy*, vol. 24, no. 11, 2017, pp. 727-734. Springer Nature, doi:10.1038/gt.2017.83.
  4. Saito, Y., Takekuma, Y., Takeshita, T., Oshino, T., & Sugawara, M. (2022). Impact of systemic dexamethasone administration on oral mucositis induced by anthracycline-containing regimens in breast cancer treatment. *Scientific Reports*, 12(12587). https://doi.org/10.1038/s41598-022-16935-4
  5. Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., & Li, Y. (2021). Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduction and Targeted Therapy, 6(263). https://doi.org/10.1038/s41392-021-00658-5