image_1_IL-17A+GM-CSF+ Neutrophils Are the Major Infiltrating Cells in Interstitial Lung Disease in an Autoimmune Arthritis Model.TIFF

Objective<p>To gain a better understanding of the pathogenesis of autoimmune arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD.</p>Methods<p>We injected curdlan in SKG mice at 8 weeks of age, and identified the presence of ILD by PET-MRI at 20 weeks post-injection and histological analysis at 22 weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22 weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed.</p>Results<p>At 20 weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b⁺Gr1⁺ neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-α. Compared with 14 weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and soluble IL-7Rα had increased at 22 weeks post-injection, whereas those of IFN-γ, IL-22, IL-6, and TNF-α remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-α, were observed in immunofluorescent-stained lung tissue.</p>Conclusion<p>We found that IL-17A⁺GM-CSF⁺ neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-α in ILD development.</p

Characteristics of 2 patients who developed active tuberculosis during TNF inhibitor treatment.

<p>Characteristics of 2 patients who developed active tuberculosis during TNF inhibitor treatment.</p

The study flowchart.

<p>RA, rheumatoid arthritis; AS, ankylosing spondylitis; TNF, tumor necrosis factor; LTBI, latent tuberculosis infection; TB, tuberculosis; TST, tuberculin skin test; QFT-GIT, QuantiFERON-TB Gold In-Tube; CXR, chest radiography.</p

LTBI test results and percentages of patients who received LTBI treatment among 476 patients.

<p>LTBI test results and percentages of patients who received LTBI treatment among 476 patients.</p

Additional file 1: of High level of interleukin-32 gamma in the joint of ankylosing spondylitis is associated with osteoblast differentiation

The protein levels of inflammatory cytokines including TNF-α, IL-1β, IL-18 and IL-22 were determined in the culture supernatant from the cells of WT or IL-32γ TG mice (A) and the cells in the absence (None) or presence of IL-32γ (B) after 1 week of OB differentiation using commercial available ELISA kits. The bars show the means ± SD of triplicate experiments. (TIFF 443 kb