During the course of the last 18 months, we have learned a lot about COVID-19, which was a new disease. It became apparent early on that one outcome of severe COVID-19 was acute respiratory distress syndrome (ARDS), with patients usually requiring mechanical ventilation. CLI caught up with Dr Anagh Vora (Senior Vice President and Chief Medical Officer of Beckman Coulter Diagnostics) to discuss the role that interleukin-6 (IL-6) plays in the development of ARDS in COVID-19 patients and how IL-6 can be used as a biomarker of more severe disease.
What is interleukin-6, and what is its normal role?
Interleukin-6 (IL-6) is a multifunctional cytokine protein produced by certain cells of the immune system, including macrophages and the adaptive T- and B-lymphocytes and endothelial cells. Cytokines are small proteins released in response to an activating stimulus, such as an infection. IL-6 can be elevated and promote inflammation in response to infections, tissue injuries, and other clinical conditions.
What is the role of IL-6 in disease?
IL-6 stimulates the inflammatory and auto-immune processes, signalling to the body that there is an infection or disease that it needs to fight. IL-6 is one of several cytokines that activate the production of acute-phase proteins, which mimic the actions of antibodies. However, in contrast to antibodies, they have broad specificity for pathogens and depend on cytokines for their production. In addition, IL-6 is an endogenous pyrogen, raising body temperature, which is believed to help eliminate infection. At higher temperatures, bacterial and/or viral infection is not as efficient, whereas the adaptive immune system operates more efficiently . So, in essence, the body ramps up to clear the disease.
What is the role of IL-6 in a cytokine storm?
A cytokine storm is an umbrella term that encompasses several disorders of immune dysregulation. A cytokine storm results from a sudden acute increase in circulating levels of different cytokines (including IL-6). Although in a normal immune response, the increase in cytokines is good because it helps eliminate the infection, in a cytokine storm, the elevated levels lead to immune cell hyperactivation and multi-organ dysfunction.
Cytokine storm syndrome (CSS) is an overwhelming and potentially life-threatening inflammatory response. It may be triggered by an infection or develop following infusion of agents targeting the immune system . Individuals with CSS experience a massive outpouring of inflammatory cytokines such as IL-6 in response to an inflammatory stimulus. The over production of these pro-inflammatory cytokines is known to be associated with an increased risk of vascular permeability, disseminated intravascular coagulation and respiratory failure .
CSS has also become increasingly recognized in COVID-19, affecting lungs and leading to acute respiratory distress syndrome (ARDS), the major cause of death in COVID-19 patients .