Targeting IL-6 can help rheumatologists, patients ‘seek shelter from the cytokine storm’
Targeting interleukin-6 can help rheumatologists manage severe, high-grade inflammation including cytokine storm, according to a presenter at the 2023 AWIR annual conference.
“We remember stories better than we remember anything,” Leonard Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, told attendees at the hybrid meeting. “My first story today is about inflammation and the role of IL-6.”
According to Calabrese, chronic inflammation, in various forms, is responsible for more than half of all deaths reported in the United States, from diabetes and metabolic syndrome, to stroke, chronic kidney disease, sarcopenia and the spectrum of autoimmune diseases.
“It is a pandemic of epic proportions,” he said.
The previous understanding of inflammation and the cytokine storm was that a genetically predetermined disorder led to the kind of inflammation that could cause functional or structural damage. However, the increased incidence of cytokine storm resulting from severe SARS-CoV-2 infection elevated the understanding of this process and changed the paradigm, according to Calabrese.
“Everything is being turned on its head,” he said, noting that there are “many different pathways” leading to this severe inflammatory event.
Calabrese added that the immune system is delicately balanced, so when a cytokine like IL-6 becomes dysregulated, severe results may occur.
“Where there is an excess, the scales tilt,” he said. “This is the space where we rheumatologists live.”
IL-6 lies at the heart of these processes because it interacts with a “wide variety of cells” involved in both innate and adaptive immunity, including, C-reactive protein, Th-17 and T-regulatory cells, Calabrese said.
“IL-6 is a master player in the cytokine network,” he added. “It has the capacity to activate or trigger a wide variety of cells through the body, both viscerosomatic and hematopoietic in origin.”
The role of IL-6 as a driver of C-reactive protein, in particular, is important because it can impact pain, mood, metabolism and weight control.
“IL-6 is a direct driver of pain,” Calabrese said.
The good news is that there is a broad spectrum of approved therapies targeting IL-6.
“The capacity to target it is increasing,” Calabrese said. “It can be inhibited by at least three pathways.”
However, the current understanding of exactly how those pathways work is still evolving. “Do they do the same thing or not? No one can answer that,” Calabrese said.
Meanwhile, given the role of IL-6 in the COVID-19 pandemic, the understanding of the cytokine storm has increased.
“However, it still lacks a true formal definition,” Calabrese said, though he noted that a clinical definition has come into focus. In addition to the inflammation, multiorgan system failure may occur, along with increases in biomarkers ranging from D-dimers and ferritin to CRP, IL-6, IL-1-beta and interferon-gamma.
Although therapies targeting IL-6 have been on the market for 2 decades, understanding how to manage inflammation and these extreme events remains a challenge for all rheumatology professionals, according to Calabrese.
“Inflammation is our stock and trade,” he said. “Sometimes we need to seek shelter from the cytokine storm.”
Collapse
Calabrese L. IL-6 in Health and Disease: Where Rheumatology Meets COVID-19 and Beyond. Presented at: Association of Women in Rheumatology annual conference; Aug. 10-13, 2023; Orlando, Florida (hybrid meeting).