New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis
Authors' conclusion
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.
Study context
- Population
- Treatment-naïve patients with early seropositive rheumatoid arthritis (RA) and healthy controlsin vitro: neutrophils from 14 ERA patients
- Participants
- 60 vs 60
- Comparison
- Treatment-naïve early RA vs healthy controls; baseline vs 3 months after conventional therapy
- ERAn = 60
- Healthy controls (HC)n = 60reference
- Outcome
- Serum IL-40
Methodological detailscase-control, in vitro experiments
- Case-control
- In vitro experiments
Main finding
As reported in the abstract
- Serum IL-40 elevated in ERA vs HC
- p<0.0001
- Serum IL-40 normalised after 3 months of therapy
- p<0.0001
- Baseline serum IL-40 correlated with RF (IgM)
- p<0.01
- Baseline serum IL-40 correlated with anti-CCP autoantibodies
- p<0.01
- Baseline serum IL-40 correlated with NETosis markers (PR3; Neutrophil elastase (NE); MPO)
- p<0.0001
- NE decreased after therapy
- p<0.01
- NE decrease correlated with decrease of serum IL-40
- p<0.05
- In vitro, neutrophils enhanced IL-40 secretion after NETosis induction
- p<0.001
- In vitro, neutrophils enhanced IL-40 secretion after IL-1β, IL-8
- p<0.05
- In vitro, neutrophils enhanced IL-40 secretion after TNF or lipopolysaccharide
- p<0.01
- Recombinant IL-40 up-regulated IL-1β, IL-6 and IL-8 in vitro
- p<0.05 for all
Original publication
New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis. RMD Open. Published 19 May 2023. doi:10.
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