Cytokine profile using plasma mRNA to mark onset of ARDS in a pediatric swine model

ABSTRACT

INTRODUCTION/HYPOTHESIS: Acute Respiratory Distress Syndrome (ARDS) is a proinflammatory acute lung injury (ALI) that leads to noncardiac pulmonary edema. In humans, ARDS can be caused directly through damage of the epithelial tissue or indirectly through damage of the endothelial tissue. Different animal models to induce ALI have been developed to mimic the complex pathophysiology of ARDS, including the use of oleic acid injections. Oleic acid induces clinical ARDS by inducing an extensive immune response, including having direct effects on innate immune cells in the lungs triggering direct inflammatory mediator production, damaging the alveoli-capillary unit with increase of alveolar leakage and impairment of gas exchange. There is a paucity of data available to characterize the use of cytokine markers in pediatric ARDS swine models. We hypothesize that in a pediatric swine model of oleic acid ARDS, pro and anti-inflammatory cytokine mRNA in plasma will display at differing concentrations than the baseline at ARDS. METHODS: Seven juvenile swine were sedated, intubated, and mechanically ventilated. ARDS was established using continuous oleic acid infusion at 0.05-0.6 mL/kg. Blood samples were taken from the femoral artery before oleic acid infusion was initiated, an hour after and at the start of ARDS. Plasma was collected and mRNA was extracted from blood mononuclear cells (MNC). Quantitative polymerase chain reaction (qPCR) was performed on samples testing for the presence of mRNA for IFN-γ, TNF-α, IL-17, IL-10, and IL-6. RESULTS: 4-5 10 mL blood samples were collected from each animal and analyzed. When compared to baseline, IFN-γ collected at ARDS onset significantly decreased by a foldchange of 0.53±0.4 at ARDS (p=0.028). IL-6 trended down at ARDS onset, although this was not significant (p=0.087). Changes of TNF-α, IL-17 and IL-10 levels at ARDS onset were not significant (p=0.740, p=0.262, and p=0.342) respectively. CONCLUSIONS: In an oleic acid swine model, ARDS is characterized by decreasing IFN-γ levels. This data does correlate with severe ARDS caused by COVID in human patients. Future studies are warranted to better characterize the role of pro-and anti-inflammatory cytokine in developing ARDS and confirm our model.