© Crown Copyright 2025, Dstl. This material is licensed under the terms of the Open Government Licence Plague is an infectious disease caused by the Gram-negative bacterium Yersinia pestis. Plague is classified as a re-emerging disease, causing periodic outbreaks in endemic countries. There is currently no licensed vaccine and, whilst antibiotics are often effective, antibiotic-resistant strains remain a concern (Lei and Kumar 2022). Late-stage plague infection can result in an excessive and detrimental delayed inflammatory response. Immune-modulatory drugs could provide a novel therapeutic approach. We have developed a simplistic in-vitro model of septicaemic plague infection using THP-1 monocyte-like cells. Cells were stimulated with formalin-inactivated Y. pestis. Pro-inflammatory cytokine release (CCL2, IL-18, IL-1β, IL-6, IL-8 and TNF-α) was measured using automated ELISA. 12 immune-modulating drugs were then added to the cell culture at different pharmacodynamically relevant concentrations before and after stimulation with inactivated Y. pestis. We show that the corticosteroids, dexamethasone and prednisolone, and MCC950 (an inflammasome inhibitor) were the most effective at reducing inflammatory signals. Niclosamide and nitazoxanide, both anti-helminthic drugs, also markedly reduced some signals. This study demonstrated the potential utility of these drugs in the treatment of plague. To the best of our knowledge there are no published studies regarding the efficacy of MCC950, niclosamide or nitazoxanide in Y. pestis infection. These drugs could represent a novel treatment adjunct for plague. Lei, C., and S. Kumar. 2022. 'Yersinia pestis antibiotic resistance: a systematic review', Osong Public Health Res Perspect, 13: 24-36.