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Type 2 cytokines and scleroderma interstitial lung disease.

Chiara Pellicano1, Lorenzo Vantaggio1, Amalia Colalillo1

  • 1Department of Translational and Precision Medicine, Sapienza University of Rome, Viale Dell'Università 37, 00185, Rome, Italy.

Clinical and Experimental Medicine
|July 1, 2023
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Summary

Elevated Type 2 (Th2) cytokine levels, particularly interleukin-4 (IL-4), are linked to interstitial lung disease (ILD) in systemic sclerosis (SSc). These Th2 cytokines may drive early-stage SSc-ILD.

Keywords:
CALIPERGround glassInterstitial lung diseaseSystemic sclerosisTh2 cytokines

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Area of Science:

  • Immunology
  • Pulmonology
  • Rheumatology

Background:

  • Interstitial lung disease (ILD) is a severe complication of systemic sclerosis (SSc).
  • Type 2 (Th2) cytokines are implicated in airway inflammation and disease progression.
  • Understanding the role of Th2 cytokines in SSc-ILD is crucial for developing targeted therapies.

Purpose of the Study:

  • To evaluate serum levels of Th2 interleukins (ILs) and chemokines in patients with SSc-ILD.
  • To investigate the correlation between Th2 cytokine levels and lung function parameters, including diffusion lung capacity for carbon monoxide (DLco) and high-resolution computed tomography (HRCT) findings.
  • To identify Th2 cytokines associated with the presence and severity of SSc-ILD.

Main Methods:

  • Serum samples from 60 SSc patients and 20 healthy controls (HC) were analyzed for IL-4, IL-5, IL-11, IL-13, IL-21, IL-31, and CXCL-13 using Bio-Plex Multiplex Immunoassays.
  • Pulmonary function tests, including DLco, and HRCT were performed on SSc patients.
  • ILD was defined by fibrotic changes on HRCT, quantified using CALIPER software.

Main Results:

  • Serum Th2 cytokine levels were significantly higher in SSc patients compared to HC.
  • Significant linear correlations were found between ground glass opacity on HRCT and IL-13, IL-21, IL-31, IL-4, and IL-5.
  • Negative correlations were observed between DLco and IL-4, as well as peripheral blood eosinophils.
  • Logistic regression identified IL-4 as independently associated with reduced DLco and the presence of ILD.

Conclusions:

  • Th2 inflammation, particularly driven by IL-4, plays a significant role in the early stages of SSc-ILD.
  • Elevated IL-4 levels are associated with impaired lung function and fibrotic changes in SSc patients.
  • These findings suggest that targeting Th2 cytokines may be a promising therapeutic strategy for SSc-ILD.