A hamster model of Jarisch-Herxheimer-like reaction in experimental leptospirosis associated with IL-6 upregulation and enhanced macrophage phagocytosis.

The Jarisch-Herxheimer reaction (JHR) is an acute inflammatory response that can occur after antimicrobial treatment of spirochetal infections, and it can lead to organ dysfunction. However, no established animal model exists for investigating its pathophysiology. In this study, female golden Syrian hamsters were experimentally infected with Leptospira interrogans and treated with aminobenzylpenicillin (ABPC) to evaluate antibiotic-associated physiological and immunological changes. Vital signs were monitored under anesthesia, and a JHR-like reaction (JHR-LR) was operationally defined as a marked change in heart rate occurring exclusively after antimicrobial administration. Bacterial burden, cytokine expression, and histopathological findings were analyzed. In vitro macrophage stimulation assays were also performed. Transient tachycardia was observed in a subset of infected hamsters following ABPC administration, most frequently at 5 days post-infection. This response was accompanied by increased IL-6 and IP-10/CXCL10 mRNA expression in the blood and enhanced macrophage phagocytosis of leptospires in the liver and spleen. In vitro, antibiotic-killed leptospires induced significantly higher IL-6 production in macrophages than live bacteria. Importantly, despite comparable bacterial burdens, marked JHR-LR occurs predominantly in animals with preserved body weight, suggesting that host physiological conditions rather than bacterial load alone influence the development of this reaction. These findings provide preliminary evidence that hamsters may develop antibiotic-associated inflammatory responses resembling JHR and support the utility of this model for future mechanistic studies.