Scientists Find Links Between Interleukin 17A and Inflammation, Organ Protection in SLE Patients

Jose Marques Lopes, PhD avatar

by Jose Marques Lopes, PhD |

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Interleukin 17A

The cytokine interleukin 17A (IL-17A), while playing a role in inflammation, may also serve a protective purpose in systemic lupus erythematosus (SLE) patients, new research shows.

The study, “IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role”, appeared in the European Journal of Rheumatology.

Immune cells produce IL-17A, which is involved in several chronic inflammatory diseases. The cytokine protects against tumor growth by modulating the immune response. However, excessive IL-17A can lead to tumor proliferation by overcoming cytokine interferon gamma (IFN-γ) tumor surveillance properties and causing local blood vessels to grow.

IL-17 inhibition benefits those with ankylosing spondylitis, a form of spinal arthritis. In mice, overexpression of IL-17A has been linked to nephritis, or inflammation of the kidney, which is caused by SLE. Importantly, increased levels of IL-17A have been reported in the sera of SLE patients. Therefore, inhibiting IL-17 could be a therapeutic pathway in SLE.

Johannes Nossent, MD, PhD, of the University of Western Australia’s School of Medicine and Pharmacology, led the research team, which evaluated the clinical associations of interleukin IL-17A in SLE patients of Northern European descent and mostly in a state of low disease activity.

The cross-sectional study involved 102 SLE patients (86 percent of them females) recruited from a regional registry. The researchers determined IL-17A levels, SLE disease activity and cumulative damage, and analyzed links between IL-17A and disease activity. They also determined autoantibody profiles and studied the interplay of immune cells across disease states and damage development in SLE patients.

Researchers found that SLE patients had higher immunoglobulin G levels and lower counts of T-cells and B-cells (immune cell types). However, IL-17A levels did not differ from the healthy controls and did not fluctuate significantly over several years of observation.

In SLE patients, IL-17A levels had no bearing on disease activity or cumulative damage, but were inversely related with age, systolic blood pressure and years of smoking. Researchers also found inverse correlations with heart damage and cancer history, which suggests a protective role for IL-17A.

Among other parameters, serum levels of IL-17A correlated with the pro-inflammatory cytokine IL-6 and immunoglobulins G and M (types of antibodies), but were inversely correlated with platelet count and pre-albumin levels, a marker of chronic renal failure.

These results support “the possible involvement of IL-17A in the inflammatory pathway in SLE, although the main source and driver of IL-17A levels remain unclear,” according to the study. However, it also shows that IL-17A “may also serve a protective purpose in SLE patients.” Overall, the “dual role of IL-17A suggests that inhibiting pro-inflammatory IL-17 effects in SLE patients could have wider and significant clinical implications.”

Future studies should analyze patients with diverse genetic backgrounds and states of disease activity, said researchers, who also urged information on the cellular source and causation of effects by IL-17A.