Interleukin-12 Is Associated with Rheumatoid Factor and Interferon-γ, but Not with Disease Activity, in Patients with Rheumatoid Arthritis

Background: IL-12 is a proinflammatory cytokine produced mainly by activated dendritic cells and macrophages that drives the differentiation of naïve T cells into Th1 cells and stimulates interferon-γ production by natural killer and T cells, thereby linking innate and adaptive immunity. Ultrasensitive quantification of IL-12 has not previously been performed in large rheumatoid arthritis (RA) cohorts, mainly due to the limited availability and high cost of these platforms. In the present study, we measured serum IL-12 using an ultrasensitive assay to systematically assess its relationship with key disease characteristics in a large, well-characterized cohort of patients with RA. Methods: A total of 216 patients with RA were recruited and underwent a comprehensive assessment of disease characteristics and disease activity. Lipid parameters and hematological markers were assessed, insulin resistance indices were calculated, and metabolic syndrome was defined according to established criteria. Arterial stiffness, carotid intima-media thickness, and plaque presence were evaluated through carotid ultrasonography. Serum IL-12 levels were quantified using Simoa (Single Molecule Array) technology. To examine the relationship between clinical and metabolic parameters and IL-12 concentrations, multivariable linear regression models were applied. Results: In multivariable analyses, serum IL-12 levels were independently associated with IFN-γ and rheumatoid factor positivity. However, no significant relationships were found between IL-12 and disease activity indices, acute-phase reactants, cardiovascular risk factors, subclinical atherosclerosis, lipid profile, glucose metabolism, or hematological parameters. Conclusions: Using an ultrasensitive assay, we found that serum IL-12 levels were associated with interferon-γ levels and rheumatoid factor positivity in patients with RA, supporting a role for IL-12 at the interface between cellular and humoral immunity. In contrast, circulating IL-12 did not appear to be a useful systemic biomarker of disease activity or of the cardiovascular and hematological comorbidities associated with RA.