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.