ArticleRMD open2023
New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis.
Article in RMD open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Salivary asprosin, IL-39, IL-40, and IL-1β levels in diabetic patients with periodontitis: A cross-sectional analysis.Clinical oral investigations · 2026Trial
- Interleukin-40 in Systemic Sclerosis: A Treatment-Sensitive Marker of Immune Modulation Rather Than Disease Activity.Clinical and translational science · 2026Article
- Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.Cell communication and signaling : CCS · 2026Article
- IL40: A Newly Described Cytokine With Conflicting Measurements and Detection Variability-Are There Different Forms?Scandinavian journal of immunology · 2026Article
- Unveiling Interleukin-40: A Novel Regulator of Macrophage and B Cell Function in Allergic Asthma.International journal of biological sciences · 2026Article
- The interactions between HLA alleles and immune indicators were associated with the risk of rheumatoid arthritis.Clinical rheumatology · 2025Article
- Comparative Investigation of Cardiac Injury Mediated by IL-40 and Oxidative Stress Markers in Pericardial Fluid and Serum.Medicina (Kaunas, Lithuania) · 2025Article
- Serum IL-40 is elevated in systemic sclerosis and is linked to disease activity, gastrointestinal involvement, immune regulation and fibrotic processes.Arthritis research & therapy · 2025Article
- Fluorescent probes in autoimmune disease research: current status and future prospects.Journal of translational medicine · 2025Review
- Inhibition of Interleukin-40 prevents multi-organ damage during sepsis by blocking NETosis.Critical care (London, England) · 2025Article
- Serum interleukin-40 increases in anti-AchR antibody-positive myasthenia gravis and correlates with disease activity.Frontiers in neurology · 2025Article
- Increased serum levels of IL-40 are associated with IgA and NETosis biomarkers in Covid-19 patients: IL-40 and infectious diseases.PloS one · 2025Article
- Cytokine Signatures as Biomarkers of Clinical Remission in Rheumatoid Arthritis.Journal of inflammation research · 2025Article
- IL-40 levels in treatment-naive and methotrexate-treated rheumatoid arthritis patients.Turkish journal of medical sciences · 2025Article
- Investigating the role of salivary Interleukin-40 levels in diagnosing periodontal diseases.Oral diseases · 2024Article
- IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro.Arthritis research & therapy · 2024Article
- IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro.Arthritis research & therapy · 2024Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInterleukin (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).
methodsIL-40 was determined in serum of treatment naïve patients with ERA at baseline (n=60) and 3 months 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.
resultsSerum IL-40 was elevated in ERA compared with HC (p<0.0001) and normalised after 3 months of therapy (p<0.0001). Baseline serum IL-40 correlated with rheumatoid factor (IgM) (p<0.01), anti-cyclic citrullinated peptide (p<0.01) autoantibodies and NETosis markers (proteinase 3; neutrophil elastase (NE); myeloperoxidase) (p<0.0001). Levels of NE significantly decreased after therapy (p<0.01) and correlated with the decrease of serum IL-40 (p<0.05). In vitro, neutrophils enhanced IL-40 secretion following NETosis induction (p<0.001) or after exposure to IL-1β, IL-8 (p<0.05), tumour necrosis factor or lipopolysaccharide (p<0.01). Recombinant IL-40 up-regulated IL-1β, IL-6 and IL-8 (p<0.05 for all) in vitro.
conclusionWe 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.