PLoS ONE (Jan 2021)

Interleukin-22 mitigates acute respiratory distress syndrome (ARDS).

  • Sharven Taghavi,
  • Olan Jackson-Weaver,
  • Sarah Abdullah,
  • Alanna Wanek,
  • Robert Drury,
  • Jacob Packer,
  • Aaron Cotton-Betteridge,
  • Juan Duchesne,
  • Derek Pociask,
  • Jay Kolls

DOI
https://doi.org/10.1371/journal.pone.0254985
Journal volume & issue
Vol. 16, no. 10
p. e0254985

Abstract

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BackgroundThe goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS).Summary background dataNo therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22.Study designARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4.ResultsIn the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham.ConclusionsIL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.