Project  LEPTOLIP

The objective of the study is to analyze, in a large sample of patients with leptospirosis (n=100), the protein (cytokines) and lipid profiles, comparing data in the acute phase and during the reevaluation at 1 month. The study relies on the COLEPT cohort, whose promoter is INSERM, and for which inclusions are completed, and data/samples are accessible to conduct the LEPTOLIP study.

During severe leptospirosis infection, some studies suggest the involvement of an exaggerated immune response, particularly cytokine-driven, leading to septic syndromes and organ failures. Studies have shown increased serum/plasma concentrations of pro-inflammatory cytokines such as IL-6, TNF-α, IL-1β, IL-8, and IL-2 in severe forms compared to moderate forms. Additionally, IL-6, IL-10, and IL-8 have been associated with increased mortality. Sepsis is a complex state characterized by significant changes in metabolic, immunological, and oxidative stress states. Several studies have shown that pro-inflammatory cytokines (such as TNF-α or IL-6) play a role in altering lipid metabolism in obesity, atherosclerosis, or diabetes. Modifications in lipid profiles have been described in various viral and bacterial sepsis contexts. During acute inflammation, decreases in HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels, as well as certain apolipoproteins, major components of lipoproteins, have been described. In the context of COVID-19, some authors have described an inverse correlation between HDL-C and LDL-C concentrations and disease severity. A study evaluating the evolution of lipid profiles remotely from sepsis has shown profile changes up to 2 years after the acute episode, potentially increasing the risk of cardiovascular complications. Beyond cholesterol levels transported by lipoproteins, their functionality has been evaluated in bacterial or viral sepsis situations. We have shown that HDL (high-density lipoproteins) lose their antioxidant and anti-inflammatory functions during the acute phases of infection, justifying a possible therapeutic approach aiming to supplement patients with functional HDL during this critical period. During leptospirosis-induced sepsis, studies with small sample sizes have shown an increase in cytokines IL-6, IL-10, and TNF-α associated with a decrease in apolipoprotein A1 and HDL-C in the acute phase in patients in intensive care, as well as changes in lipid profile. This pro-atherogenic lipid profile was normalized at 4 months post-infection, except for HDL-C levels, which remained decreased. However, these data, mainly focusing on cholesterol levels, were obtained from a small number of patients in a single study, indicating a need to further investigate such work in terms of both the number of patients and the details of the lipid profile characteristics, particularly regarding lipoprotein functionality. Furthermore, correlations between lipid profile and inflammatory profile (cytokines) have never been studied in leptospirosis.