The IL 12 Cytokine Family in Cardiovascular Disease: Context Dependent Signaling, Immune Remodeling, and Therapeutic...

Cardiovascular diseases (CVDs) are increasingly recognized as immune-mediated disorders in which cytokines regulate leukocyte recruitment, activation, and tissue repair. This review summarizes the roles of the interleukin-12 (IL-12) cytokine family, including IL-12, interleukin-23 (IL-23), interleukin-27 (IL-27), and interleukin-35 (IL-35), in vascular and myocardial pathology. We highlight the heterodimeric structure and shared-subunit biology of these cytokines, which produce overlapping receptor usage and downstream Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling, contributing to substantial functional pleiotropy. Mechanistic evidence is reviewed showing how IL-12 family cytokines regulate endothelial activation, adhesion pathways, leukocyte recruitment, macrophage polarization, and immune-stromal crosstalk, thereby influencing extracellular matrix turnover and cardiovascular remodeling. Disease-specific findings are discussed in atherosclerosis, angiotensin II-associated hypertension, myocardial infarction, pulmonary hypertension, and diabetic cardiomyopathy. Across these conditions, cytokines may exert either protective or pathogenic effects depending on timing, cellular source, receptor context, and tissue environment. We further examine translational implications for biomarker development and therapeutic targeting, emphasizing the challenge of distinguishing prognostic associations from causal signaling. Overall, IL-12 family cytokines act as context-dependent immunoregulatory nodes in CVD.