Therapeutic effects of an anti-IL-6 antibody in fungal keratitis: Macrophage inhibition and T cell subset regulation

Immune modulation plays a critical role in the pathogenesis of fungal keratitis (FK). However, the immune cell-mediated processes linking the innate immune response to the adaptive immune response are incompletely elucidated. IL-6 plays crucial roles in infectious and inflammatory processes in the cornea, regulating not only mononuclear macrophage differentiation but also lymphocyte activation, and IL-6 might be a useful target for immune intervention in FK. The frequencies of macrophages and T cells increased upon infection and were correlated with the severity of ocular pathogenesis. Additionally, protein profiling revealed that the expression of IL-6 and associated cytokines/chemokines was upregulated. Furthermore, anti-IL-6 intervention suppressed disease progression by reducing macrophage infiltration in the cornea and Th1, Th17, and Treg cell infiltration in draining lymph nodes (DLN) in an animal model of FK. Tocilizumab (TCZ), an antibody specific for IL-6, reduced the signal transducer and activator of transcription 3 (STAT3) activation in vivo and in vitro. In summary, fungal infection promoted macrophage and T cell activation via IL-6-mediated transcellular signaling to regulate immune cell migration and cytokine production, further demonstrating the role of IL-6 and providing a potential clinical therapeutic target in FK.