Human visceral leishmaniasis: decrease in serum cholesterol as a function of splenic parasite load.

Abstract

Kala azar or human visceral leishmaniasis (VL) is a debilitating disease associated with hepato–splenomegaly, anaemia, thrombocytopaenia and immunosuppression (Pearson et al., 1983). The predominant causative agent, Leishmania donovani, replicates within the reticulo-endothelial system of the liver, and the liver parenchyma, although initially unaffected, is slowly damaged as the disease progresses (Alsaffar and Al Mudhaffar, 1979). Consequently, hepatic dysfunction — showing as coagulation defects and changes in the serum concentrations of several liver-specific enzymes — is typical of VL (Chakroborty et al., 1949). As the liver is the main source of cholesterol biosynthesis in mammals (Tennent et al., 1957), hepatic dysfunction may lead to low serum concentrations of cholesterol and this may lead to further morbidity. Hypocholesterolaemic men tend to have significantly fewer circulating lymphocytes, total T cells, helper T-cells and CD8+ cells than hypercholesterolaemic men (Muldoon et al., 1997). In their meta-analysis of 19 cohort studies covering 68,406 deaths, Jacobs et al. (1992) found an inverse correlation between blood concentrations of cholesterol and mortality from respiratory and gastro-intestinal diseases (most of which are of infectious origin). Subsequently, in a 15-year follow-up study of >120,000 individuals, Iribarren et al. (1998) found a strong inverse association between blood concentrations of cholesterol and the risk of being admitted to hospital because of an infectious disease. It appears that hypercholesterolaemia may confer a survival advantage in many, if not all, infectious diseases. In an experimental study, Netea et al. (1996) showed that mice deficient in receptors for low-density lipoprotein (LDL) and with endogenous hypercholesterolaemia were protected against infection with Gram-negative micro-organisms, the lower cholesterol levels observed being associated with increased mortality. In tuberculosis, serum concentrations of cholesterol, high-density lipoprotein and LDL can be used as indirect markers of disease severity, with relatively low levels indicative of advanced disease (Rao, 2009). Akerlund et al. (1986) described how, in patients with severe bacterial infections, total serum cholesterol concentrations were lowered during the acute stage of their disease. Decreased serum cholesterol has already been reported in patients with VL (Lal et al., 2007). In experimentally infected hamsters, Banerjee et al. (2009) not only demonstrated a significant decrease in membrane cholesterol during the active stage of L. donovani infection but also found that the liposomal delivery of cholesterol offered significant protection. These observations led to the present study, which was focused on cholesterol and not other lipids. In this study, since cellular cholesterol and serum cholesterol are in dynamic equilibrium (Chobanian et al., 1962), serum concentrations of cholesterol in Indian patients with VL were determined as surrogate markers of cellular cholesterol. Subsequently, the relationship between the observed serum concentrations of cholesterol and the parasite burdens in the patients’ spleens was explored.