Background/Purpose: Interleukin-40 (IL-40) is a newly described cytokine related to malignancies and immunity function. We have previously shown that IL-40 is up-regulated in early stages of rheumatoid arthritis (RA) and associates with processes that are thought to fuel the immune response. As the period preceding clinically apparent RA has not yet been fully described with respect to clinical biomarkers, we aimed to investigate IL-40 in individuals at-risk of RA development and its involvement in immune regulation in peripheral blood mononuclear cells (PBMCs).

Methods: IL-40 was analysed in the serum of individuals at-risk of RA (n=179, defined as patients with arthralgia with no clinical arthritis who are either carriers of anti-citrullinated protein antibodies, ACPA, or meeting the EULAR definition of clinically suspect arthralgia at baseline) and at the time of arthritis manifestation in patients who progressed to clinical arthritis (n=25). IL-40 was determined in the serum of age and sex-matched healthy controls (n=60). In vitro experiments were performed on PBMCs from at-risk individuals (n=10). Levels of IL-40 and IL-6 were measured by commercially available ELISA kits.

Results: IL-40 is up-regulated in at-risk individuals compared to healthy controls(p< 0.0001) and the levels of IL-40 are higher in the serum of double-positive (ACPA/rheumatoid factor) compared to double-negative at-risk individuals (p< 0.05). Out of 175 at-risk individuals, 25 developed clinical arthritis (with median 8.17 months of follow up); however, we have not found a significant difference in the levels of IL-40 at baseline, and at the time of arthritis manifestation. In vitro, PBMCs from at-risk individuals exposed to recombinant IL-40 strongly enhance the secretion of IL-6 in a dose-dependent manner when compared to unstimulated cells (IL-40: 10 ng/ml, p< 0.05; 50, 100, 250 ng/ml, p< 0.01). Furthermore, the application of NFkB inhibitor to the PBMCs prior to the exposure to IL-40 significantly reduced the secretion of IL-6 when compared to IL-40 treated cells without inhibition (p=0.004).

Conclusion: Here we show for the first time that IL-40 is elevated in the serum of individuals at-risk of RA. Moreover, results imply that systemically elevated IL-40 induces the pro-inflammatory response in PBMCs at-risk individuals via NFkB dependent pathway.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-newly-described-cytokine-interleukin-40-is-increased-in-the-serum-of-individuals-at-risk-of-rheumatoid-arthritis-and-induces-an-inflammatory-response-in-mononuclear-cells/