4. DISCUSSION
Fatal SFTS and severe and critically ill COVID-19 patients develop a pathological state termed cytokine release syndrome.[1, 3-11]
Cytokine release syndrome can be triggered by infections and is characterized by rapid and prolonged systemic elevation of inflammatory cytokines and chemokines, and IL-6 is a proinflammatory cytokine and a key cytokine in cytokine release syndrome-induced mortality.[1, 3-11]
Serum IL-10 is an important anti-inflammatory cytokine.[12] However, the serum IL-10 concentration was significantly higher in fatal SFTS, severe and critically ill COVID-19, and H5N1 patients and, like IL-6, can predict poor outcomes in SFTS and COVID-19 patients (Figures 1 and2 ).[5, 7, 9, 10]
In this study, we found that TGF-β concentrations were significantly lower in fatal SFTS and severe and critical COVID-19 patients (Figures 1 and 2 ). Namely, the hyperproduction of IL-6 and IL-10, which is a feature of cytokine storms, and the low production of TGF-β have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients (Figures 1and 2 ).
Furthermore, IL-10 was elevated earlier than IL-6, and TGF-β was decreased later than IL-10 in SFTS and COVID-19 patients (Tables 1 and 2 ).
When we blocked IL-10 signalling using an antibody against the IL-10 receptor, the production of IL-6 was decreased, and the production of TGF-β was increased (Figures 3, 4, and 5 andSupplemental table 5, 6, and 7 ).
IL-10 is usually known as an anti-inflammatory cytokine [12]. However, IL-10 can also be an immune-activating and proinflammatory cytokine in some autoimmune diseases, cancers, and severe and critically ill COVID-19 patients. Patients with fatal SFTS and H5N1 present with dramatically elevated serum IL-10 concentrations that correlate with disease severity.[5, 7, 9-11]
Fatal SFTS and severe and critically ill COVID-19 patients present with dramatically elevated serum levels of IL-10 and IL-6 and dramatically decreased serum levels of TGF-β that correlate with disease severity.
When we blocked the signal of IL-10 using an antibody against the IL-10 receptor, IL-6 was decreased and TGF-β was elevated in the THP-1-cell study (Figures 3-5 ).
Therefore, we suggest that IL-10 can induce the production of IL-6 and inhibit the production of TGF-β in cytokine storms and might play a pathological role in SFTS and COVID-19 disease progression and also propose that IL-10 may be a potential target for reducing SFTS and COVID-19 mortality.