Animal models of anemia of inflammation: Methodological advances, limitations, and translational applications

Anemia of inflammation (AI) represents one of the most prevalent secondary anemias in clinical practice, frequently complicating a wide spectrum of chronic inflammatory diseases. Given its highly heterogeneous etiology and complex pathophysiological mechanisms, the establishment of rational and high-fidelity animal models is vital for elucidating the core mechanisms of AI and optimizing clinical diagnostic and therapeutic strategies. This narrative review provides a structured categorization of current AI animal models into three major paradigms: sterile inflammation models, disease-specific models, and genetically engineered models. We provide an in-depth comparative analysis of their underlying modeling principles, methodological protocols, and characteristic phenotypic profiles, while comprehensively evaluating their respective translational advantages and intrinsic limitations. Furthermore, we discuss the prospective applications of these models in deciphering pathomechanisms, validating therapeutic targets, and developing interventional strategies. To enhance reproducibility and translational relevance, we propose a streamlined phenotyping panel and a model selection framework. The precise selection and rational application of these tailored models will contribute to improved reliability of fundamental AI research and accelerate its translational progression from bench to bedside.