Circulating Levels of Adiponectin, Leptin, Fetuin-A and Retinol-Binding Protein in Patients with Tuberculosis: Markers of Metabolism and Inflammation

Abstract

BackgroundWasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4).MethodsThe plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals ( = no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation ( = active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA).ResultsIn the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P = 0.0033 and P = 0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP.ConclusionsOur data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines.

Adiponectin in inflammatory and immune-mediated diseases

“…The results of animal studies linking APN to COPD-like disease are contradictory, with reports of a spontaneous emphysema-like phenotype, but also of protection from tobacco-induced emphysema, using different strains of APN KO mice [51–53]. Altered levels of APN are also present in other conditions with pulmonary involvement, such as tuberculosis and infection with non-tuberculous mycobacteria [105, 106], but again the meaning of this association remains unclear.…”

Why are kids with lupus at an increased risk of cardiovascular disease?

“…It defends the VSMC against injury and decreases VSMC migration, reducing the migration of macrophages and their transformation into foam cells [193,209]. Recent work shows low levels of serum adiponectin in women with SLE, that levels are inversely correlated with measures of vascular function [31,[197][198][199] and that its actions result in increased serum levels of IL1 and IL1RA and decreased levels of TNF-α and IL6 [210]. However, our group has shown a tendency towards increased adiponectin levels in patients with JSLE, associated with an increase in cIMT [30].…”

“…It is associated with an atherogenic lipid profile [221][222][223][224], acting to inhibit apoptosis of VSMCs and to protect against their calcification. Low levels appear to impair macrophage function [210,225,226]. It interacts with free fatty acids to activate Toll-like receptor-4 (TLR4) and increase insulin resistance [221,227,228].…”

Type 2 diabetes mellitus coincident with pulmonary or latent tuberculosis results in modulation of adipocytokines

“…Low plasma leptin and high adiponectin levels are linked with wasting and inflammation in pulmonary TB [40-41]. In addition, resistin is considered to be a surrogate biomarker for pulmonary TB while PAI-1 is known to be present at higher concentrations in pulmonary TB [42-43].…”