Elucidating the mechanistic basis by which IL-6’s pleiotropic effects govern disease trajectory—encompassing progression kinetics, severity gradients, and temporal dynamics—alongside delineating the molecular architecture underpinning IL-6’s pathogenic involvement across diverse disorders, will ultimately advance our understanding of canonical IL-6 receptor signaling pathways and trans-signaling mechanisms in autoimmune pathogenesis, infectious disease progression, epithelial barrier integrity, and tumorigenesis. This evidence concerns the gene IL6 and infectious disease.