A Potential Role of Vitamin D on Platelet Leukocyte Aggregation and Pathological Events in Sepsis: An Updated Review

Abstract

Vitamin D deficiency and sepsis are both significant global health problems. Insufficient vitamin D is considered to be a pathogenically relevant factor of sepsis-related deaths; however, a causal relationship has not yet been demonstrated. Recently, vitamin D has been an exciting field of research owing to the identification of vitamin D receptors on many extra skeletal tissues and cells, suggesting an unexpected role on body physiology, beyond its effects on bone homeostasis. However, while the role of vitamin D on bone health is widely understood and has been successfully translated into clinical applications and public health policies, recent evidence supporting its role in other physiological and pathological processes has not been fully established. In sepsis, there is an induction of local intracellular vitamin D activity by most immune cells, including lymphocytes, macrophages, neutrophils, and dendritic cells, as well as vascular endothelial cells, to ensure efficient clearance of infective microorganisms and mediate anti-inflammatory and tolerogenic effects. The literature suggests an association between low vitamin D levels and sepsis, but clinical trials have yielded contradictory results. A greater understanding of this role may improve disease management. This article reviews the available knowledge regarding vitamin D in immune function, emerging literature regarding the association between its deficiency and sepsis, as well as presenting its potential effect on platelet leukocyte aggregations (PLAs), a significant pathology in sepsis. It also summarizes clinical trials involving vitamin D supplementation during critical illness and sepsis and addresses the impact of relevant factors of sepsis pathogenesis on the efficacy of vitamin D supplementation, which could contribute to the reported inconsistencies. Looking ahead, further studies are required to uncover the possible modulatory relationship between vitamin D and sepsis to define better cut-offs for its levels, proper timing of its administration, and the optimum dosage for best management.

The Significance of Systemic Immune-Inflammatory Index and Platelet-Neutrophil Ratio on Early Mortality in Septic Shock Patients and their Association with Vitamin D and Parathyroid Hormone Ratio

“…Interestingly, vitamin D deficiency was significantly associated with the low level of SII and PNR, especially in the first 48 hours of septic shock, despite similar C-reactive protein levels. It is known that platelets have their own vitamin D receptor and vitamin D plays a pivotal role in antithrombogenicity [27]. Also, platelet-leukocyte aggregates are liberally generated during sepsis in the circulation and tissues, and they are related with worse outcomes, as mentioned above [27].…”

“…It is known that platelets have their own vitamin D receptor and vitamin D plays a pivotal role in antithrombogenicity [27]. Also, platelet-leukocyte aggregates are liberally generated during sepsis in the circulation and tissues, and they are related with worse outcomes, as mentioned above [27]. Vitamin D deficiency may lead to platelet consumption and may result in a decrease in SII and PNR.…”

Novel therapeutic approaches to treat inflammatory conditions with glucocorticoid and calciferol nanoparticles in vivo and in vitro

“…Although vitamin D deficiency occurs in up to 98% of critical care unit patients with sepsis, its effects on the pathogenesis and the outcome of the disease are not yet understood even though both phenomena frequently coexist clinically. [113] This association between vitamin D deficiency and sepsis has also been observed in children and neonates. [114] Importantly, some studies show an increased mortality among severe vitamin D deficiency patients.…”

“…[115], [116] An induction of local intracellular vitamin D activity by immune cells has been observed in sepsis, resulting in efficient pathogen clearance and anti-inflammatory and tolerogenic effects. [113] Early clinical data indeed suggested a role of vitamin D in preventing and attenuating infections.…”

“…[118], [119] In another study, high cholecalciferol doses were administered to ICU individuals leading to a substantial increase in calcitriol serum concentrations supplementation. [113] This highlights the difficulty to understand which patient could benefit from calcitriol treatment and how vitamin D influences sepsis.…”