Blood levels of cytokines, immune signaling molecules, differ with AS

Four cytokines seen as possible disease-driving factors

Lindsey Shapiro avatar

by Lindsey Shapiro |

Share this article:

Share article via email
An illustration shows blood in a dropper next to four vials that also contain blood.

Certain immune signaling molecules belonging to a family of proteins called cytokines were at altered levels in the blood of men with ankylosing spondylitis (AS) under treatment compared with men in the general population, a study found.

Three cytokines with known pro-inflammatory functions — IL-17A, CXCL10, and CXCL16 — were higher in patients’ blood, while a fourth, IL-31, was at lower levels.

Researchers think these findings will contribute to a better understanding of the disease-driving, or pathogenic, role that cytokines might play in AS.

The study, “Evaluation of interleukins (IL-1α, IL-1Ra, IL-12, IL-17A, IL-31, and IL-33) and chemokines (CXCL10 and CXCL16) in the serum of male patients with ankylosing spondylitis,” was published in International Immunopharmacology.

Recommended Reading
ankylosing spondylitis diet | Ankylosing Spondylitis News | Banner for Janneke Phung's column,

How my life has changed since my ankylosing spondylitis diagnosis

Study into factors that might be a cause of AS development

Dysregulated immune reactions are among the mechanisms believed to contribute to AS, a chronic inflammatory disease affecting joints of the spine.

Cytokines are a family of immune signaling molecules that are widely implicated in inflammatory and autoimmune diseases, and they also have been recognized as AS biomarkers.

Medications that inhibit particular cytokines are used to treat AS and other immune-related conditions. This includes tumor necrosis factor (TNF) inhibitors such as Humira, Cimzia, and Enbrel, or interleukin-17 (IL-17) blockers like Cosentyx and Taltz.

Still, many molecules belong to the cytokine family, some of which generally are believed to have pro-inflammatory effects and others to be anti-inflammatory. A holistic picture of which cytokines contribute to AS pathogenesis still is needed.

Researchers at the University of Baghdad compared blood levels of a group of eight pro-inflammatory and anti-inflammatory cytokines between 94 men with AS and 91 age-matched healthy men as controls.

Six of these cytokines — IL-12, IL-17A, IL-33, IL-1-alpha, CXCL10, and IL-1 receptor antagonist — previously have been studied in the context of AS, but little is known about the potential role of the other two, IL-31 and CXCL16, in the inflammatory disease, the scientists reported.

High levels of three cytokines tied to significantly higher risk of disease

Blood levels of three cytokines — IL-17A, CXCL10, and CXCL16 — were significantly increased in AS patients relative to controls, and each was associated with a significantly higher risk of AS by 22%, 78%, and 14%, respectively. All three of these cytokines are known to be pro-inflammatory.

Conversely, IL-31 was significantly decreased in patients, and it associated with about an 11% lower risk of the disease. While dysregulated IL-31 signaling has been identified in other inflammatory disorders, the cytokine remains understudied in AS.

All four of these cytokines ultimately were found to be of value in distinguishing AS patients from healthy controls, with a diagnostic accuracy ranging from around 70% to 88%.

Levels of these cytokines were not influenced by clinical factors such as disease duration, disease activity, or certain other markers linked to AS. Levels of IL-17A were significantly lower in patients treated with anti-TNF medications plus other disease-modifying anti-rheumatic drugs (DMARDs), compared with patients treated with either anti-TNF medications or other DMARDs.

Additional analyses indicated that the four dysregulated cytokines appear to interact with one another, which researchers believe may “confirm the functional relationship between these cytokines in the pathogenesis of AS.”

Researchers emphasized that as this study included only AS patients on active treatments that could affect immune function, its results cannot necessarily be generalized to newly diagnosed and untreated patients.

“Therefore, follow-up evaluation of cytokines in the diagnostic and treatment periods is warranted to gain a greater understanding of the relationship between cytokines and the pathogenesis of AS,” they wrote.