Patterns of Mutual Associations Within the IL-12 Cytokine Family in Systemic Sclerosis Patients: A Pilot Study

Objectives: This study aimed to investigate the associations among cytokines of the IL-12 family in patients with systemic sclerosis (SSc) and to evaluate their relationships with the pro-inflammatory cytokines TNF-α and IL-6, the latent form of TGF-β1 (LAP-bound, without prior sample activation), clinical parameters, and disease subtypes. Methods: Concentrations of IL-12p70, IL-12p40, IL-23, IL-27, IL-35, IL-39, TNF-α, and IL-6 were measured in serum, whereas latent TGF-β1 concentrations were determined in plasma obtained from 60 patients with systemic sclerosis (SSc) and 21 age- and sex-matched healthy controls. Results: Compared with healthy controls, patients with SSc exhibited significantly elevated levels of IL-12p40, IL-23, and IL-35, whereas IL-27, TNF-α, and TGF-β concentrations were significantly reduced. Correlation analysis revealed significant negative associations between latent TGF-β1 and IL-6, IL-27, and IL-35. Significant positive correlations were observed between TNF-α and IL-6, TNF-α and IL-12p40, IL-35 and IL-12p40, IL-23 and IL-12p40, and IL-12p40 with both IL-6 and IL-12p70. No significant associations were identified between the investigated cytokines and the Medsger severity score, patient age, anti-centromere antibody (ACA) status, anti-topoisomerase I antibody (Scl-70) status, the presence of pulmonary fibrosis, or diffusing capacity of the lungs for carbon monoxide (DLCO). In contrast, IL-35 levels demonstrated significant moderate negative correlations with both the modified Rodnan Skin Score (mRSS) (ρ = -0.35, p < 0.01) and disease duration (ρ = -0.30, p < 0.05). Conclusions: These findings may indicate the presence of a complex network of associations among IL-12 family cytokines in systemic sclerosis.