Background and Aim : Several viral pathogens including SARS CoV 2 are associated with the lung inflammation. The severity of disease is associated with the production of a cytokine storm (CS) by the macrophages inside the host cell post-viral attack. Since the cytokine storm is the life-threatening through the elevated levels of circulating cytokines, factors targeting these pro-inflammatory proteins may be an ideal strategy for the management of various inflammatory disorders like coronavirus disease. In this study, the intranasal administration of spore probiotic was investigated to modulate the lung inflammatory response of Balb/c mice triggered by the viral pathogen-associated molecular pattern polyinosinic acid- polycytidylic acid (poly (I:C)). Methods : Male BALB/c (approximately 20 g, 8 12 weeks old) were obtained from the Razi Institute (Mashhad, Iran) and housed in a conventional animal house with 12-hours dark/light cycles. Water and pelleted food were provided ad libitum. The animals were anesthetized by isoflurane inhalation and 20 μl of heat-inactivated spore probiotic cells (10 CFU/mL) were administered intranasally for 5 consecutive days. On days 5-7 mice received three doses of 20 μl poly (I:C) (1 mg/ml). Mice were euthanized on day 10 i.e. 24 h after the last intranasal treatment. Control animals received PBS instead of bacterial suspensions. Inflammatory modulatory activity of spore probiotic was determined based on bronchoalveolar tissue lavage (BALF) cytokines, lung histology, and the lung wet-to-dry (W/D) weight ratio. Results : Pro-inflammatory cytokines including TNF-?, IL-1? and IL-6 were reduced 2.5, 1.8, and 14.5 folds while the anti-inflammatory cytokines i.e. TGF-? and IL-10 were increased 1.06 and 2.2 folds in the mice received spore probiotic, respectively. Compared with the control group (6.7?±?0.15), the wet/dry weight ratios of lung tissues in the probiotic group (5.75?±?0.12) were significantly decreased(p<0.05).The effect of probiotic treatment on lung pathology was revealed that lung injury and the number of mononuclear cells were significantly reduced in animals treated with probiotic(p<0.05). Conclusion : Spore probiotics are probably promising agents to modulate life-threating inflammation associated with viral infections like SARS CoV 2

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