Leutragin Inhibits Expression of Cytokines, Including Interleukin-6, in a “Cytokine Storm” Model in C57BL/6Y Mice with Induced Acute Respiratory Distress Syndrome

Abstract

This study aims to investigate effects of leutragin, an analogue of endogenous hexapeptide dynorphin 1-6, on the expression of pro-inflammatory cytokines and type I interferons in an experimental model of fatal acute respiratory distress syndrome (ARDS) in C57BL/6Y mice. The expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor (TNF-α), interferons α (IFN-α) and β (IFN-β) in the lungs was assessed by real-time PCR. The induction of ARDS using α-galactosylceramide and E. coli lipopolysaccharide led to a multifold increase in the expression of the cytokines in the lungs. The administration of leutragin in a combined mode — intramuscular injection plus inhalation — led to a statistically significant decrease in the mRNA levels of cytokines within three hours after the start of administration. The average mRNA levels of IL-6, a key cytokine in the development of severe acute respiratory syndrome, decreased by 4.7 times (p<0.01) to reach values close to those observed in intact animals. Given the crucial role of elevated IL-6 concentrations in the development of severe forms of COVID-19, the use of leutragine for suppressing “cytokine storm” syndromes may be an effective approach to the treatment of this coronavirus infection.