Pro- or anti-inflammatory properties of cytokines in COVID-۱۹: which offer better protection against disease

Pro- or anti-inflammatory properties of cytokines in COVID-۱۹: which offer better protection against diseaseI read the article by Al-Mquter et al. that compared circulating levels of ۳ cytokines(IL-۶, IL-۲۵ and IL-۳۵) amongst healthy controls(HC) and patients with COVID-۱۹. They reported a significant increase in the serum concentration of these cytokines in patients versus HC(۱). Their results confirmed again that assessment of cytokine profiles could be used as COVID-۱۹ markers and may also provide practical implications for disease treatment. Nonetheless, understanding the role of cytokines in COVID-۱۹ is complicated because of the complex nature of cytokine networks and the pathogenesis of COVID-۱۹(۲). IL-۶ is one of the first cytokines produced during COVID-۱۹ and increasing evidence suggests that its alteration may be associated with disease outcome. IL-۶ is a pleotropic cytokine and has both pro- and anti- inflammatory effects. Therefore, it appears to operate in protective or pathological immunity to COVID-۱۹. IL-۶ can promote immune processes associated with resistance to different pathogens including COVID-۱۹. It contributes to host defense via different pathways, including the stimulation of acute phase responses and hematopoiesis. Nonetheless, dysregulated and persistent synthesis of IL-۶ can be resulted to the onset and development of pathological conditions. These different effector functions may be associated with different concentration of IL-۶ that may result from different signaling pathwaysIL-۶ signaling includes at least three distinct pathways: cis-signalling; trans-signalling and trans-presentation. It seems that IL-۶ trans-signalling and trans-presentation are probably responsible for severe progressive COVID-۱۹. These signaling pathways can trigger diffuse inflammation at various levels. Conversely, IL-۶ cis-signalling mediates negative feedback mechanisms on proinflammatory cytokines, including suppression of their production, stimulation of their decoy receptors, and inhibition the maturation of Th۱۷ cells. Circulatory IL-۶ in COVID-۱۹ patients reaches the peak level at advanced stages around two weeks of disease. Elevated IL-۶ (e.g., > ۱۰۰-۱۲۰ pg/mL) levels in critical COVID-۱۹ may reflect augmented IL-۶ cis-signalling in an attempt to exert homeostatic functions, although there is no general consensus on this issue(۳).

Keywords:

Coronavirus disease , Cytokines , inflammation