tetano
Editor, Senior Moderator
Front Immunol
. 2026 Jun 25:17:1828107.
doi: 10.3389/fimmu.2026.1828107. eCollection 2026.
Antibodies against interleukin-10 receptor reduce IL-6 and TNF-α levels and increase TGF-β levels in patients with severe fever with thrombocytopenia syndrome virus and SARS-CoV-2 infection
Su Yeon Kang[SUP] #[/SUP][SUP] 1 [/SUP], Jeong Rae Yoo[SUP] #[/SUP][SUP] 2 [/SUP], EunJin Bae[SUP] #[/SUP][SUP] 1 [/SUP], Joowan Kim[SUP] #[/SUP][SUP] 3 [/SUP], Yejin Park[SUP] 4 [/SUP], Misun Kim[SUP] 2 [/SUP], Miyeon Kim[SUP] 2 [/SUP], Hyo-Jin Ro[SUP] 3 [/SUP], Daehee Hwang[SUP] 5 [/SUP], Jeong-Yeon Lee[SUP] 1 [/SUP], Dongcharn Cho[SUP] 1 [/SUP], Huy Chau Nguyen[SUP] 6 [/SUP], Hoai Jaclyn Hallam[SUP] 6 [/SUP], Sang Taek Heo[SUP] 2 [/SUP], Nam-Hyuk Cho[SUP] 3 [/SUP], Kyung-Mi Lee[SUP] 4 [/SUP], Andrew G Letizia[SUP] 6 [/SUP], Keun Hwa Lee[SUP] 1 [/SUP]
Affiliations
Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe, often fatal, disease characterized by hyperinflammation and features of a cytokine storm. Hyperproduction of both IL-10 and IL-6 and low TGF-β production can generate a cytokine storm, with IL-10 playing a particularly important role. To investigate the role of IL-10 in patients with SFTS, we analyzed the phenotypes of macrophages, cytokines, and signaling pathways in patients with mild to fatal SFTS and found that the population of HLA-DR[SUP]+[/SUP]CD86[SUP]+[/SUP] macrophages was increased, the population of CD163[SUP]+[/SUP]CD206[SUP]+[/SUP] macrophages was decreased, the levels of IL-10 (p < 0.0001), IL-6 (p < 0.0001), TNF-α (p=0.1056), and CCL1 (p=0.1533) were increased, TGF-β (p=0.0104) was increased, and Smad3 and P-Smad3 were highly expressed in patients with fatal SFTS. We also investigated the role of IL-10 in THP-1-derived macrophages infected with SFTSV or SARS-CoV-2, treated with lipopolysaccharide (LPS), or treated with serum from patients with fatal SFTS. We found that blocking IL-10 signaling can decrease the population of HLA-DR[SUP]+[/SUP]CD86[SUP]+[/SUP] cells, increase the population of CD163[SUP]+[/SUP]CD206[SUP]+[/SUP] cells, reduce IL-6 and TNF-α production, increase TGF-β production and induce the expression of Smad3 and P-Smad3 in SFTSV- and SARS-CoV-2-infected and LPS-induced THP-1 cells. Additionally, IL-10 receptor blockade can reduce IL-10 and IL-6 production in THP-1 cells treated with serum from patients with fatal SFTS. Therefore, we suggest that HLA-DR[SUP]hi[/SUP]CD86[SUP]hi[/SUP] macrophages may contribute to pathological activity and that CD163[SUP]hi[/SUP]CD206[SUP]hi[/SUP] macrophages may play a critical role in the protection of effector functions against SFTSV and SARS-CoV-2 infection. IL-10 could serve as a prognostic target, and antibodies against the IL-10 receptor could represent a potential immune-based intervention against a cytokine storm in patients with fatal SFTS and severe/critical COVID-19.
Keywords: IL-6; SARS-CoV-2; TGF‐β; TNF-α; antibodies against interleukin-10 receptor; severe fever with thrombocytopenia syndrome.
. 2026 Jun 25:17:1828107.
doi: 10.3389/fimmu.2026.1828107. eCollection 2026.
Antibodies against interleukin-10 receptor reduce IL-6 and TNF-α levels and increase TGF-β levels in patients with severe fever with thrombocytopenia syndrome virus and SARS-CoV-2 infection
Su Yeon Kang[SUP] #[/SUP][SUP] 1 [/SUP], Jeong Rae Yoo[SUP] #[/SUP][SUP] 2 [/SUP], EunJin Bae[SUP] #[/SUP][SUP] 1 [/SUP], Joowan Kim[SUP] #[/SUP][SUP] 3 [/SUP], Yejin Park[SUP] 4 [/SUP], Misun Kim[SUP] 2 [/SUP], Miyeon Kim[SUP] 2 [/SUP], Hyo-Jin Ro[SUP] 3 [/SUP], Daehee Hwang[SUP] 5 [/SUP], Jeong-Yeon Lee[SUP] 1 [/SUP], Dongcharn Cho[SUP] 1 [/SUP], Huy Chau Nguyen[SUP] 6 [/SUP], Hoai Jaclyn Hallam[SUP] 6 [/SUP], Sang Taek Heo[SUP] 2 [/SUP], Nam-Hyuk Cho[SUP] 3 [/SUP], Kyung-Mi Lee[SUP] 4 [/SUP], Andrew G Letizia[SUP] 6 [/SUP], Keun Hwa Lee[SUP] 1 [/SUP]
Affiliations
- PMID: 42427492
- PMCID: PMC13347219
- DOI: 10.3389/fimmu.2026.1828107
Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe, often fatal, disease characterized by hyperinflammation and features of a cytokine storm. Hyperproduction of both IL-10 and IL-6 and low TGF-β production can generate a cytokine storm, with IL-10 playing a particularly important role. To investigate the role of IL-10 in patients with SFTS, we analyzed the phenotypes of macrophages, cytokines, and signaling pathways in patients with mild to fatal SFTS and found that the population of HLA-DR[SUP]+[/SUP]CD86[SUP]+[/SUP] macrophages was increased, the population of CD163[SUP]+[/SUP]CD206[SUP]+[/SUP] macrophages was decreased, the levels of IL-10 (p < 0.0001), IL-6 (p < 0.0001), TNF-α (p=0.1056), and CCL1 (p=0.1533) were increased, TGF-β (p=0.0104) was increased, and Smad3 and P-Smad3 were highly expressed in patients with fatal SFTS. We also investigated the role of IL-10 in THP-1-derived macrophages infected with SFTSV or SARS-CoV-2, treated with lipopolysaccharide (LPS), or treated with serum from patients with fatal SFTS. We found that blocking IL-10 signaling can decrease the population of HLA-DR[SUP]+[/SUP]CD86[SUP]+[/SUP] cells, increase the population of CD163[SUP]+[/SUP]CD206[SUP]+[/SUP] cells, reduce IL-6 and TNF-α production, increase TGF-β production and induce the expression of Smad3 and P-Smad3 in SFTSV- and SARS-CoV-2-infected and LPS-induced THP-1 cells. Additionally, IL-10 receptor blockade can reduce IL-10 and IL-6 production in THP-1 cells treated with serum from patients with fatal SFTS. Therefore, we suggest that HLA-DR[SUP]hi[/SUP]CD86[SUP]hi[/SUP] macrophages may contribute to pathological activity and that CD163[SUP]hi[/SUP]CD206[SUP]hi[/SUP] macrophages may play a critical role in the protection of effector functions against SFTSV and SARS-CoV-2 infection. IL-10 could serve as a prognostic target, and antibodies against the IL-10 receptor could represent a potential immune-based intervention against a cytokine storm in patients with fatal SFTS and severe/critical COVID-19.
Keywords: IL-6; SARS-CoV-2; TGF‐β; TNF-α; antibodies against interleukin-10 receptor; severe fever with thrombocytopenia syndrome.