High IL-18 Levels Associated With Interstitial Lung Disease in RA

Increased plasma interleukin (IL)-18 levels were associated with the presence of interstitial lung disease in patients with rheumatoid arthritis (RA), and within this patient population, IL-18 levels were higher for patients with interstitial lung disease vs patients without, according to a study published in the Scandinavian Journal of Rheumatology.

The investigators of this cross-sectional study sought to determine whether high IL-18 levels are associated with the presence of interstitial lung disease in patients with RA.

The study sample included a total of 312 patients with RA who were enrolled in the database of the Kyoto University Rheumatoid Arthritis Management Alliance cohort. Enzyme-linked immunosorbent assay was used to measure plasma IL-18 levels, while chest radiography and computed tomography (CT) findings were used to diagnose patients with suspected interstitial lung disease.

The study investigators compared IL-18 levels in patients with RA with interstitial lung disease and in patients with  RA without interstitial lung disease. Using multivariate logistic regression modeling, the investigators analyzed the association between interstitial lung disease and various biomarkers, including IL-18, as well as confounding variables, such as history of tobacco use. The diagnostic performance of IL-18 to estimate the presence of interstitial lung disease in RA was evaluated for sensitivity and specificity using receiver operating characteristics curve analysis.

Of 312 participants with RA, 26 (8.2%) had complications of interstitial lung disease. Plasma IL-18 levels were higher for participants with interstitial lung disease (721±481.4 pg/mL; P <.001) than for participants without interstitial lung disease (436.8±438.9 pg/mL; P <.001). In multivariate logistic regression analyses, IL-18, Krebs von den Lungen-6, glucocorticoid dose, and anti-cyclic citrullinated peptide antibody titre were independently associated with the presence of interstitial lung disease.IL-18 levels for detecting interstitial lung disease in patients with RA demonstrated 65.3% sensitivity and 76.3% specificity, which was determined by analyzing the area under the curve (0.73).

Limitations of the study included only performing chest CT scans on patients with suspected interstitial lung disease according to chest x-ray screening results, as well as data on pulmonary symptoms and function not being available to the investigators. Due to the cross-sectional nature of the study, causality could not be determined between increased IL-18 levels and presence of interstitial lung disease.

The investigators concluded that the presence of interstitial lung disease in patients with RA was associated with increased plasma IL-18 levels, and suggested that further studies are needed to understand the pathological relationship between IL-18 and interstitial lung disease etiology.  

Multiple authors declare associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.

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Reference                    

Matsuo T, Hashimoto M, Ito I, et al. Interleukin-18 is associated with the presence of interstitial lung disease in rheumatoid arthritis: a cross-sectional study [published online September 30, 2018.] Scand J Rheumatol. doi:10.1080/03009742.2018.1477989.