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Increased interleukin-37 associated with adult-onset Still's disease
Increased levels of interleukin-37 are positively correlated with disease activity in adult-onset Still’s disease, according to findings published in Arthritis Research and Therapy.
“[Interleukin (IL)-37], a newly discovered member of the IL-1 family, has been identified as a natural inhibitor of immune responses,” Huihui Chi, of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and colleagues wrote. “However, whether immunosuppressive features of IL-37 contribute to the pathogenesis of autoinflammatory diseases such as [adult-onset Still’s disease (AOSD] is still unclear.”
To analyze IL-37 levels and their association with AOSD, as well as to determine the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs), the researchers collected blood samples from 62 patients with the disorder to compare with those of 50 health controls. IL-37 levels were determined through enzyme-linked immunosorbent assay, and correlations between serum levels and disease activity were analyzed using the Spearman’s correlation test.
In addition, Chi and colleagues stimulated PBMCs from 10 patients with AOSD with recombinant human IL-37 protein. TNF-, IL-6, IL-10, IL-1 and IL-18 levels were determined through quantitative real-time-PCR and enzyme-linked immunosorbent assay.
According to the researchers, patients in the AOSD cohort showed a significantly higher IL-37 protein level than their healthy peers. In addition, among patients with the disease, IL-37 levels were correlated with systemic score, laboratory values, IL-1, IL-18, and IL-10. The production of proinflammatory cytokines, including IL-6, IL-1, TNF- and IL-18, in PBMCs was markedly attenuated after recombinant human IL-37 stimulation in patients with AOSD. The expression of IL-37 was related to patients with AOSD who demonstrated fever, skin rash, lymphadenopathy, splenomegaly, myalgia and arthralgia.
“In the present study, we showed that the upregulation of IL-37 was positively correlated with AOSD disease activity, indicating its involvement in AOSD pathogenesis, and it may become a novel disease activity biomarker,” Chi and colleagues wrote. “Our results derived from the cell-based functional assay suggest that IL-37 may participate in the course of AOSD through the reduction of proinflammatory cytokines. Further studies are required to confirm the regulatory mechanism of IL-37 in the pathogenesis of AOSD and extend the present findings.” – by Jason Laday
Disclosure: The researchers report no relevant financial disclosures.