Effect of mustard analogs on cytokine profile in rodents: A systematic review and meta-analysis

Mustard analogs (sulfur and nitrogen forms) are toxic agents that may damage immunity. This meta-analysis investigates the impact of mustard analogs on cytokine profiles in rodent models, emphasizing trends and inconsistencies observed in previous studies. A total of 21 relevant studies that evaluated the effect of mustard analogs on cytokines were screened. Data were extracted, and effect size and heterogeneity were assessed using random-effects models, Cochrane Q, and I² statistics. The analysis revealed significant elevations in levels of IL-1α, IFN-ϒ, IL-1β, IL-6, and TNFα and a reduction in the level of IL-10 following mustard exposure. The subgroup analysis showed that sulfur mustard analogs increased IL-1β, IL-6, IFN-γ, and TNF-α levels, while IL-10 levels decreased. Nitrogen mustard analogs also elevated IL-1α, IL-1β, and IL-6. Short-term exposure increased most cytokines, with a decrease in IL-10. In the medium term, all cytokines were elevated except IL-10, which was reduced. Long-term exposure sustained higher levels of IL-1α and IL-6. Analysis of serum, plasma, and BALF samples confirmed significant rises in most cytokines, with IL-10 reduced. Injection routes consistently led to increased cytokines IL-1α, IL-1β, IL-6, IFN-γ, TNF-α and decreased IL-10, whereas vapor and liquid touch routes primarily increased IL-6. It is concluded that mustard analogs induce notable inflammatory responses in rodent models. Among these, sulfur mustard exhibits more extensive systemic effects compared to nitrogen mustard, resulting in more severe inflammation. Additionally, the route of administration substantially influences the severity of the inflammatory response. The exposure length and sample type also affect the cytokine levels, which may mandate the development of targeted treatments to counteract these effects.