## 1 Introduction  
Half-marathon (21.0975 km) is an increasingly popular recreational activity. Its diffusion is in part related to the fact that half-marathon requires less powerful training than the marathon [1]. Nonetheless, one reason for its importance in terms of clinical risk is that half-marathon is performed by a growing number of people in the world, although it still remains a powerful training, which might potentially retain adverse health repercussions. In fact, studies focusing on the role of exercise and inflammatory response have underlined that several cytokines increased after a competitive marathon [2]. In this context, it is interesting to assess the role of sphingolipids, bioactive lipids that regulate diverse cell functions, since the activity of sphingomyelinases (Sphingolipid metabolizing enzymes) is increased under inflammation and oxidative stress [3]. Thus, ceramides have been associated with oxidative stress status and inflammatory processes [3]. However, changes of ceramide concentration after a half-marathon race have never been examined. Moreover, to the best of our knowledge, the relationship that may exist between bioactive lipids and markers of inflammation/immune response has never been studied in trained subjects following acute physical exertion such as a half-marathon. In this context, how changes in the balance between inflammatory mediators, immune response or lipid may contribute to the response in the post-race phase and affect the health status of subjects participating in such events also remains unclear. Thus, we aimed to evaluate levels of bioactive lipids related to inflammation signaling pathways, and to this purpose, we studied plasma ceramides, diacylglycerolglycerol and SM. These lipids can modulate the activity of intracellular enzymes (e.g., those involved in insulin signaling). In detail:  
* Ceramides exert their influence in cellular stress response, inflammatory processes, apoptosis and signaling pathways. They are also accumulated in skeletal muscle, promoting insulin resistance and oxidative stress, contributing to the onset and development of cardiometabolic diseases and renal dysfunction [4]. Several inflammatory cytokines may generate ROS and also induce ceramide formation in several cell types [5]. * Diacylglycerols (DAG) act as second messengers affecting signal transduction from many immune cell receptors and can be produced and metabolized through multiple mechanisms. Moreover, DAG induces the hydrolysis of SM to ceramides. * Sphingomyelins (SM) are reservoirs for other sphingolipids, influencing cell signaling through their structural role in lipid rafts or through the effects of their catabolic mediators (e.g., ceramides) [6]. Changes in SM concentration directly impact cell membrane physiology by modifying its transmission signal. Thus, we aimed to evaluate the changes in plasma levels of these bioactive lipids in healthy runners performing a half-marathon, at the end of the race and after 24 h recovery, and their associations with new recently proposed and common biomarkers of immune activation, which are:  
* The soluble fractalkine CX3 CL1, a potent chemoattractant of T cells and monocytes, which has a recognized role in both immune cell migration and adhesion and is involved in many inflammatory processes and diseases [7]. * Vascular endothelial growth factor (VEGF) is a multifactorial cytokine that derives from endothelial cells and pericytes in response to hypoxia, and is implicated in angiogenesis and microvascular hyperpermeability events [8]
* Interleukin-6 (IL-6), which is generated by different cell types (e.g., macrophages, endothelial cells and T cells). The contraction of skeletal muscle may induce the release of IL-6 into the interstitium as well as into blood in response to an exercise burst. Moreover, IL-6 may modulate the immunological and metabolic reactions to exercise [9].