Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice

Abstract

Introduction: T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods: Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue.Results: LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-κB, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2α volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors.Conclusions: Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile.

Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1

“…Our study showed that ERM, albeit not JSM or PC, induced IL-10 and decreased TNF and IL-17. Importantly, a recent study showed that anti-IL-17 pretreatment protects mice from the acute lung injury (59). These antiinflammatory effects of ERM are dependent on DEL-1 and, at least in part, on its anti-neutrophil recruitment action.…”

Severe Acute Respiratory Syndrome–Coronavirus-2 Infection and Patients With Lung Cancer: The Potential Role of Interleukin-17 Target Therapy

“…The use of IL-17 antibody is well-recognized; it is currently approved in the treatment of psoriatic arthritis. Moreover, the therapeutic role of IL-17 antibodies has already been established not only in different cancer types 16 but also in the treatment of lung infection with H1N1 virus, 19 in acute respiratory distress syndrome, 4,20 and pulmonary fibrosis. 21 From this analysis, and in the context of the global pandemic, there seem to be some theoretical elements to testing the potential utility of IL-17 antibodies in patients with lung cancer and COVID-19 in a clinical trial setting, with its potentially high social impact and given the lack of specific validated treatments.…”

<p>Inflammatory Cytokine: IL-17A Signaling Pathway in Patients Present with COVID-19 and Current Treatment Strategy</p>

“…Anti-IL-17A humanized monoclonal antibodies such as secukinumab (AIN457) (approved fully human IL-17-specific IgG1k monoclonal antibody) and Ixekizumab (LY2439821) (under a phase III clinical trial for psoriasis) are well-known and recognized treatment options for psoriasis. 44,[59][60][61] These anti-IL-17A monoclonal antibodies are also utilized in different inflammatory diseases, including ARDS, 13 rheumatism, 61 and pulmonary fibrosis. 62 Moreover, patients presenting with COVID-19 show elevated serum IL-6, which correlates with respiratory failure.…”

“…10,11 In turn, IL-17A acts by activating inducible nitric oxide synthase (iNOS) and inducing the expression of macrophages, IL-1β, IL-6, IL-8, TNFα, and several chemokines, which collaborate to potentiate the inflammatory process of ARDS. 13 Elevated Th17 (as well as Th1) responses or enhanced IL-17-related pathways are also observed in MERS-CoV and SARS-CoV patients. 14,18 ARDS is not commonly due to the viral load but due to an exuberant immune response, and results in cytokine release syndrome (CRS).…”

“…[9][10][11][12] Secondary to a large amount of inflammatory cell infiltration and the cytokine storm, the alveolar-capillary membrane becomes congested, damaged, and leaky, allowing increased movement of water and proteins from the intravascular space to the interstitial space. 13 In turn, pulmonary edema, lung failure, and death ensue. 9 Taking this a step further, severely infected patients with ARDS have elevated serum levels of IL-1B, IL1RA, IL-6, IL-7, IL-8, IL-17, IL-9, IL-10, fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFNγ), granulocyte colony-stimulating factor (G-CSF), interferonγ-inducible protein (IP10), monocyte chemoattractant protein (MCP1), macrophage inflammatory protein-1α (MIP1α), platelet-derived growth factor (PDGF), tumor necrosis factor (TNFα), and vascular endothelial growth factor (VEGF) ( Table 1).…”