Attenuated effects of rivastigmine in induced cytokine storm in mice

Abstract

Background: A cytokine storm is a serious clinical condition that complicates infectious diseases, for example, coronavirus disease 2019 (COVID-19), and non-infectious diseases such as autoimmune diseases and cancer and may often lead to death. The patients who are affected by the cytokine storm are almost always severe/critical and at risk for acute respiratory distress syndrome or eventually death. Pro-inflammatory cytokines such as interleukin 6 (IL-6), IL-1 beta, and tumor necrosis factor alpha (TNF-α) have been repeatedly shown to be related to the COVID-19 disease severity and mortality. In this study, our objective was to evaluate the attenuated effect of rivastigmine (RA) in a cytokine storm in Swiss Albino mice in which the cytokine storm was induced by lipopolysaccharide (LPS) and to explore their effects on IL-1 β, IL-6, and TNF-α levels. Methods: This study was carried with 60 male Swiss albino mice that were divided equally and randomly into six groups as follows: • Group AH: Apparently healthy control group which received no induction, not treated. • Group LPS: Induced using LPS at 5 mg/kg and no treatment administered. • Group DMSO: Induced and treated with 1% dimethyl sulfoxide (DMSO). • Group RA: Induced and treated with 0.5 mg/kg RA. • Group MPA: Induced and treated with 50 mg/kg methylprednisolone (MPA). • Group RMPA: Induced and treated with 0.25 mg/kg rivastigmine and 25 mg/kg of methylprednisolone. All the mice were treated with drugs or vehicles for three consecutive days before LPS induction. The mice were then injected with LPS intraperitoneally at a dosage of 5 mg/kg for systematic inflammatory stimulation. After 48 hours of LPS induction, all the mice were euthanized by light anesthesia with chloroform, and blood was collected for the quantitative determination of IL-1β, IL-6, and TNF-α levels using the enzyme-linked immunosorbent assay (ELISA) technique. Results: Administration of LPS to Swiss albino mice caused a significant elevation of IL-1β, IL-6, and TNF-α levels than in the healthy control group. Significant reduction of these parameters were observed in the RA and MPA groups when compared with those in the non-treated group. Conclusion: RA was found to be effective in attenuating the induced cytokine storm by suppressing IL-1β, IL-6, and TNF-α levels, and the results with RA were comparable to that of MPA. A combination of half-doses of both RA and MPA administered together shows no obvious advantage when compared with that of each of them alone.

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