Abstract
Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs. To elucidate the potential role of rifaximin (RIF) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5 mg/kg lipopolysaccharide (LPS) without intervention. The other group received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 50 mg/kg RIF, and a combination of 25 mg/kg RIF with 25 mg/kg MP. The second part of the study involves the therapeutic potential; all groups received similar doses of drugs to that received in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RIF and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with rifaximin and its combination with MP ameliorates the tissue damage in both lung and liver tissues following LPS induction. In conclusion, rifaximin showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms, and its combination with methylprednisolone showed additive/ synergistic action.