TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Abstract

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52–5.73); mild vs. survived severe cases 4.02 (1.84–8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12–0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23–76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects.

Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus

“…In the center of the cytokine storm is a classic pro-inflammatory factor called tumor necrosis factor-α (TNF-α), and a crucial component of the inflammatory response is interleukin-6 (interleukin −6, IL-6) ( Hirano, 2021 ; Pandey and Karupiah, 2022 ). The influenza virus infection can cause many organ lesions, even death, by upregulating the levels of TNF-α, IL-6, and other inflammatory cytokines and inducing a strong pro-inflammatory immune response ( Alagarasu et al, 2021 ). Secretory IgA (sIgA) is the antibody with the highest proportion at mucosal sites and has a stronger antiviral neutralizing capacity ( Berthold and Wormald, 2020 ).…”

Identifying Hub Genes and miRNA-mRNA Regulatory Networks in Mice Infected with H1N1 Influenza Virus

“…More importantly, we found that DEGs were enriched in TNF signaling pathways, suggesting that TNF is an important indicator of H1N1 infection. Multiple meta-analyses have also revealed that TNF gene polymorphisms are associated with H1N1 virus susceptibility and severity of infection [22][23][24][25][26]. On the other hand, no elevated levels of TNFrelated factors were detected in the plasma of pregnant women vaccinated against the H1N1 virus.…”

Exploring the active ingredients and pharmacological mechanisms of the oral intake formula Huoxiang Suling Shuanghua Decoction on influenza virus type A based on network pharmacology and experimental exploration

“…Therefore, TLR4 or CD14 may bind to ssRNA, activating MyD88, and then the activation of MyD88 transmitting signals and activating NF-κB p65, which increases the production of proinflammatory cytokines of IFN-γ, IL-6, and chemokines of MCP-1, MIP-1α, and IP-10, while inhibiting the production of anti-inflammatory cytokine of IL-10 ( Zhu et al, 2018 ; Ma et al, 2020 ). Besides, clinical research has shown that the levels of cytokines IL-6 and IL-17 are related to the disease severity of H1N1 infection patients, especially the IL-6 may be a biomarker for predicting fatal outcomes of H1N1 infection ( Alagarasu et al, 2021 ). Hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor that regulates many downstream target genes ( Huang et al, 2022 ).…”