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. 2018 Jul 10;9:1547. doi: 10.3389/fimmu.2018.01547

Table 2.

New immunomodulatory approaches to treat influenza A virus (IAV) infection.

Potential target/approach Possible intervention Effect Reference
Histones Anti-histone antibodies Prevents lung inflammation and damage induced by histones Ashar et al. (161)
NETosis

  1. Cl-amidine

  2. Tetrahydroisoquinolines (both tested on NETosis, effect on IAV yet to be determined)

 Prevents lung injury mediated by NET

  1. Kusunoki et al. (164)

  2. Martinez et al. (163)
ILC2 To be determined Promotes airway epithelium repair Califano et al. (171)
Nox2

  1. Cholestanol-conjugated gp91ds-TAT

  2. Apocynin [also as reactive oxygen species (ROS) scavenger]

  3. Ebselen (also as ROS scavenger and glutathione peroxidase mimetic)

 Inhibits Nox2 activity

  1. To et al. (177)

  2. Ye et al. (154)

  3. Oostwoud et al. (184)
Tumor necrosis factor (TNF) Etanercept Prevents TNF-mediated lung injury and edema Shi et al. (205)
IL-6 Administration of IL-6 Inhibits cell death of neutrophils; limits CD8+ T-cell-induced lung injury Dienz et al. (206); Pyle et al. (208)
IL-27 Administration of IL-27 at recovery phase (5–10 days post-infection) Promotes recovery and improves lung immunopathology Liu et al. (214)
Type III IFN Administration of type III IFN Controls IAV replication by type III IFN signaling pathways Davidson et al. (222); Kim et al. (224)
PGE2 signaling

  1. AH6809 (EP2 antagonist)

  2. GW627368X (EP4 antagonist)

 Restores type I IFNs induction which are suppressed by PGE2 in macrophages Coulombe et al. (231)
TLR4 signaling TLR4 antagonists (a. Eritoran and b. FP7) Ameliorates TLR4-mediated lung injury

  1. Shirey et al. (248)

  2. Perrin-Cocon et al. (249)
TIRAP antagonism Peptide 2R9 Inhibits multiple TLR signaling Piao et al. (250)
TLR2 signaling Anti-TLR2 antibody Inhibits TLR2 signaling mediated lethality Shirey et al. (251)
TLR3 signaling Polysaccharides isolated from R. isatidis Down regulates TLR3 expression to inhibit hypercytokinemia Li et al. (255)
TLR7 signaling MENK Down regulates TLR7 expression and reduces lung pathology Tian et al. (256)