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Higher IL-10/TNF-α and IL-10/IL-1β expression ratios in mouse compared to hamster.Differential expression independently of the Leptospira strain.Neutralisation of IL-10 led to increased susceptibility in Leptospira-infected mouse.IL-10 has a role in regulation of IL-1β during leptospirosis.IL-10 neutralization did not interact with TNF-α expression level.Leptospirosis is a severe zoonosis which immunopathogenesis is poorly understood. We evaluated correlation between acute form of the disease and the ratio of the anti-inflammatory cytokine IL-10 to the pro-inflammatory TNF-α and IL-1β expression during the early phase of infection comparing resistant mice and susceptible hamsters infected with two different species of virulent Leptospira. The IL-10/TNF-α and IL-10/IL-1β expression ratios were higher in mouse compared to hamster independently of the Leptospira strain, suggesting a preponderant role of the host response and notably these cytokines in the clinical expression and survival to leptospirosis. Using an IL-10 neutralization strategy in Leptospira-infected mouse model, we also showed evidence of a possible role of this cytokine on host susceptibility, bacterial clearance and on regulation of cytokine gene expression.