Reducing of the respiratory effects of dizocilpine by recombinant interleukin-1β in experiment

Abstract

BACKGROUND: For a deeper understanding of the pathogenesis of COVID-19, it is necessary to study the mechanisms that implement the influence of pro-inflammatory cytokines on the processes of regulation of the external respiratory system. In experiments on anesthetized rats, the effect of the pro-inflammatory cytokine interleukin-1β on the respiratory effects of dizocilpine (MK-801), which has an inhibitory effect on neurotransmitter systems involved in the control of the respiratory system, was studied. It was considered that, first of all, dizocilpine is a highly effective non-competitive NMDA-type glutamate receptor blocker.

AIM: The objectives of the study were to identify the effect of the influence of dizocilpine on the parameters of the breathing pattern and to assess the degree of change in this effect when dizocilpine was administered against the background of an elevated systemic level of interleukin-1β.

MATERIALS AND METHODS: The study was performed on 24 anesthetized tracheostomy spontaneously breathing rats. To register the volume-time parameters of external respiration, a pneumotachographic technique was used. In the process of processing the obtained results, the value of the recorded parameter was determined immediately before the introduction of MK-801 and 1 min after its introduction

RESULTS: At a dosage of 0.1 mg/kg, dizocilpine was found to cause a reversible short-term decrease in respiratory rate, tidal volume, and minute respiratory volume. It has been shown that this effect of dizocilpine does not appear after intravenous administration of interleukin-1β (at a dosage of 2 μg/kg). The results obtained confirm the assumption about the effect of an elevated systemic level of interleukin-1β on the state of neurotransmitter systems involved in the control of respiration.

CONCLUSIONS: Based on the correlation of the obtained results with the literature data, an assumption was made about a change in the state of NMDA-type glutamate receptors under the influence of pro-inflammatory cytokines, which may be one of the mechanisms of cardiorespiratory dysfunctions observed in a systemic inflammatory reaction accompanied by hypercytokinemia.

Keywords

respiration / interleukin-1β / dizocilpine (MK-801) / NMDA receptors / cytokine storm

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