By analyzing new findings from the literature on immunometabolism during the transition period, as well as classical concepts, we aim to propose a new approach to the inflammation paradigm in cows transitioning from gestation to lactation. The purpose of this review, based on data from scientific articles and reviews, is to characterize the immunometabolism of the transition period, highlighting the main characteristics of the inflammatory response in dairy cows and listing the mechanisms that govern inflammatory tone and coordinate the resolution of inflammation, with a view of new paradigms and analysis of non-classical pathways. We also seek to analyze inflammation and the role of mitochondria and the endoplasmic reticulum in the genesis of diseases, proposing approaches for modulating inflammatory tone. This review analyzes the classical theoretical approach using mechanistic views anchored in knowledge produced in other species and based on new evidence from the bovine field, determining new paradigms. This study highlights the constant inflammatory condition during the transition period and its effect on metabolism and demonstrates the role of dysregulation of inflammation resolution as a central factor in the genesis of diseases. Purinergic and cholinergic anti-inflammatory pathways have been little explored in cattle, but it is believed that the role of these pathways in maintaining homeostasis represents a great opportunity for understanding and modulating the phenomenon of inflammation in dairy cows. Dysregulation of the stress axis shows elucidative potential regarding the dysregulation of inflammatory resolution, with mitochondrial health and endoplasmic reticulum stress being dividing factors between homeorhetic and pathological states. Modulating inflammation and establishing inflammatory resolution presents challenges with classic anti-inflammatory drugs due to the paradoxical role of prostaglandin E2 in inflammation and resolution. Phytoactives offer new possibilities for modulating inflammation without disrupting inflammatory resolution and ensuring antioxidant effects, associated with strategies for formulating less inflammatory diets.
Fritzen et al. (2025) studied this question.