{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T16:29:25Z","timestamp":1787416165418,"version":"build-2736575974"},"reference-count":29,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ministry of Education Youth and Sports of the Czech Republic","award":["SVV 260523"],"award-info":[{"award-number":["SVV 260523"]}]},{"DOI":"10.13039\/501100003243","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"crossref","award":["023728"],"award-info":[{"award-number":["023728"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003243","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"crossref","award":["NU21-05-00276"],"award-info":[{"award-number":["NU21-05-00276"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Biobanks and Biomolecular Resources Research Infrastructure Consortium","award":["BBMRI-CZ LM2018125"],"award-info":[{"award-number":["BBMRI-CZ LM2018125"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2023,5,7]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Interleukin (IL)-40 is a new cytokine related to immune system function and malignancies. Recently, an association of IL-40 with rheumatoid arthritis (RA) and externalisation of neutrophil extracellular traps (NETosis) was found. As neutrophils are implicated in RA development, we investigated IL-40 in early stages of RA (ERA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IL-40 was determined in serum of treatment na\u00efve patients with ERA at baseline (n=60) and 3\u2009months after initiation of conventional therapy and in healthy controls (HC; n=60). Levels of IL-40, cytokines and NETosis markers were measured by ELISA. NETosis was visualised by immunofluorescence. In vitro experiments were performed on peripheral blood neutrophils from ERA patients (n=14). Cell-free DNA was analysed in serum and supernatants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum IL-40 was elevated in ERA compared with HC (p&lt;0.0001) and normalised after 3\u2009months of therapy (p&lt;0.0001). Baseline serum IL-40 correlated with rheumatoid factor (IgM) (p&lt;0.01), anti-cyclic citrullinated peptide (p&lt;0.01) autoantibodies and NETosis markers (proteinase 3; neutrophil elastase (NE); myeloperoxidase) (p&lt;0.0001). Levels of NE significantly decreased after therapy (p&lt;0.01) and correlated with the decrease of serum IL-40 (p&lt;0.05). In vitro, neutrophils enhanced IL-40 secretion following NETosis induction (p&lt;0.001) or after exposure to IL-1\u03b2, IL-8 (p&lt;0.05), tumour necrosis factor or lipopolysaccharide (p&lt;0.01). Recombinant IL-40 up-regulated IL-1\u03b2, IL-6 and IL-8 (p&lt;0.05 for all) in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We showed that IL-40 is significantly up-regulated in seropositive ERA and decreases after conventional therapy. Moreover, neutrophils are an important source of IL-40 in RA, and its release is potentiated by cytokines and NETosis. Thus, IL-40 may play a role in ERA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2022-002894","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T08:01:05Z","timestamp":1684483265000},"page":"e002894","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis"],"prefix":"10.1136","volume":"9","author":[{"given":"Ad\u00e9la","family":"Navr\u00e1tilov\u00e1","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic"},{"name":"1st Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Be\u010dv\u00e1\u0159","sequence":"additional","affiliation":[{"name":"Department of 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