Role of IL-27 in COVID-19: A Thin Line between Protection and Disease Promotion

Cytokine storm is usually described as one of the main reasons behind COVID-associated mortality. Cytokines are essential protein molecules engaged in immune responses; they play a critical role in protection against infections. However, they also contribute to inflammatory reactions and tissue damage, becoming a double-edged sword in the context of COVID-19. Recent studies have suggested various cytokines and chemokines that play a crucial role in the immune response to SARS-CoV-2 infection. One such cytokine is interleukin 27 (IL-27), which has been found to be elevated in the blood plasma of patients with COVID-19. Within this study, we will explore the role of IL-27 in immune responses and analyze both the existing literature and our own prior research findings on this cytokine in the context of COVID-19. It affects a wide variety of immune cells. Regardless of the pathological process it is involved in, IL-27 is critical for upholding the necessary balance between tissue damage and cytotoxicity against infectious agents and/or tumors. In COVID-19, it is involved in multiple processes, including antiviral cytotoxicity via CD8+ cells, IgG subclass switching, and even the activation of Tregs.