leptin and Tuberculosis

Topics: Animals; Comorbidity; Diabetes Mellitus; Global Health; HIV Infections; Humans; Infections; Leptin; Malaria; Malnutrition; Measles; Obesity; Protein-Energy Malnutrition; Risk Factors; T-Lymphocytes; Tuberculosis

This objective of this study was to determine benefit of one month combined supplementation (zinc, vitamin A, fish oil) along with anti-tuberculosis drugs (ATD) on increasing serum leptin levels and decreasing tumor necrosis factor-alpha (TNF-alpha) in children with tuberculosis (TB). A quasi experimental study was conducted on 22 children (aged 5-14 years) with a positive acid-fast bacilli (AFB) smear. The children were divided into 2 groups. A history, physical examination, anthropometric measurements, serum leptin levels, TNF-alpha levels, retinol and zinc levels were examined in all subjects before and after treatment. Nutritional supplementation and ATD were given to group I while ATD only were given to group II. The change in leptin, TNF-alpha, retinol and zinc levels were analyzed with the Mann-Whitney test, while a t-test was used to determine changes in body mass index (BMI). Group I had a higher significant increase in serum leptin levels than group II (p=0.034). Group I had a significantly greater decrease in TNF-a levels than group II (p=0.032). No significant differences in retinol or zinc levels were seen between the two, but both groups had an increase after treatment. Both groups had a significant increase in BMI (p=<0.001) post-treatment compared to pre-treatment. Supplementation with zinc, vitamin A and fish oil is associated with a significant increase in leptin levels and a significant decrease in TNF-alpha levels among children treated for TB. No significant benefit was seen in BMI among children receiving supplementation compared to those without it, although ATD resulted in a significant increase in BMI in both groups.

Topics: Adolescent; Antitubercular Agents; Body Weights and Measures; Child; Child Nutrition Disorders; Child, Preschool; Dietary Supplements; Drug Therapy, Combination; Female; Fish Oils; Humans; Leptin; Male; Tuberculosis; Tumor Necrosis Factor-alpha; Vitamin A; Zinc

Topics: Adipokines; Adiponectin; Aged; Case-Control Studies; Ghrelin; Humans; Leptin; Middle Aged; Prospective Studies; Resistin; Risk Factors; Singapore; Tuberculosis

The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host's inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE.. Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA.. We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48-14.11] ng/mL vs 3.08 [0.54-6.34] ng/mL; p = 0.028).. We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.

Topics: Adult; Antigens, Neoplasm; Case-Control Studies; Female; Humans; Leptin; Male; Mitogen-Activated Protein Kinases; Prospective Studies; Tuberculosis; Weight Loss

To investigate factors that determine the response to Bacille Calmette-Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to infections or newborn's nutritional status.. The study was conducted in an urban area, in Makassar, Indonesia. At baseline, 100 mother and newborns pair from high and low SES communities were included. Intestinal protozoa, soil transmitted helminths, total IgE, anti-Hepatitis A Virus IgG and anti-Toxoplasma IgG were measured to determine exposure to infections. Information on gestational age, birth weight/height and delivery status were collected. Weight-for-length z-score, a proxy for newborns adiposity, was calculated. Leptin and adiponectin from cord sera were also measured. At 10 months of age, BCG scar size was measured from 59 infants. Statistical modelling was performed using multiple linear regression.. Both SES and birth nutritional status shape the response towards BCG vaccination at 10 months of age. Infants born to low SES families have smaller BCG scar size compared to infants born from high SES families and total IgE contributed to the reduced scar size. On the other hand, infants born with better nutritional status were found to have bigger BCG scar size but this association was abolished by leptin levels at birth.. This study provides new insights into the importance of SES and leptin levels at birth on the development of BCG scar in 10 months old infants.. Investiguer les facteurs qui déterminent la réponse à la vaccination par le BCG en milieu urbain en ce qui concerne le statut socioéconomique (SSE), l'exposition prénatale aux infections ou l’état nutritionnel du nouveau-né. MÉTHODES: L’étude a été menée dans une zone urbaine, à Makassar, en Indonésie. Au départ, 100 paires mère-nouveau-né issues de communautés à statut social élevé et faible ont été incluses. Les protozoaires intestinaux, les helminthes transmis par le sol, les IgE totales, les IgG anti-virus de l'hépatite A et anti- Toxoplasma ont été mesurés pour déterminer l'exposition aux infections. Des informations sur l’âge gestationnel, le poids/taille à la naissance et l’état d'accouchement ont été collectées. Le z-score poids-pour la taille, un indicateur indirect de l'adiposité du nouveau-né a été calculé. La leptine et l'adiponectine provenant de sérum des cordons ont également été mesurées. A l’âge de 10 mois, la taille des cicatrices de BCG a été mesurée chez 59 nourrissons. La modélisation statistique a été réalisée à l'aide d'une régression linéaire multiple. RÉSULTATS: Le statut socioéconomique et l’état nutritionnel à la naissance déterminent la réponse à la vaccination par le BCG à l’âge de 10 mois. La taille des cicatrices de BCG est plus petite chez les nourrissons nés de familles à statut socioéconomique faible comparée à celles chez ceux de familles à statut socioéconomique élevé et les IgE totales ont contribué à la réduction de la taille de ces cicatrices. En revanche, les bébés nés avec un meilleur état nutritionnel avaient une taille de cicatrice du BCG plus grande, mais cette association était supprimée par les niveaux de leptine à la naissance.. Cette étude fournit de nouvelles informations sur l'importance du SSE et des niveaux de leptine à la naissance sur le développement d'une cicatrice du BCG chez des nourrissons âgés de 10 mois.

Topics: Antibodies; BCG Vaccine; Cicatrix; Female; Humans; Indonesia; Infant; Leptin; Linear Models; Male; Nutritional Status; Social Class; Tuberculosis; Urban Population

Obesity affects immune function by increasing the number of T helper lymphocytes, which may reduce the risk of tuberculosis (TB) infection. However, the effect of obesity on TB development has not been extensively studied. This nationwide population-based cohort study investigated the effect of obesity on TB development in Taiwanese adults.. We included 46 028 adult participants (age ⩾18 years) from three rounds (2001, 2005 and 2009) of the Taiwan National Health Interview Survey. Obesity and overweight were defined as a body mass index (BMI) ⩾27 and 24-26.9 (kg/m. In total, 241 new cases of active TB occurred during the study period. Obesity (adjusted odds ratio [AOR], 0.43; 95% confident interval [CI], 0.28-0.67) and overweight (AOR, 0.67; 95% CI, 0.49-0.91) were associated with lower risk of incident TB, after adjusting for demographic characteristics and comorbidities. There was a linear dose-response relation of BMI with active TB incidence (AOR per unit change in BMI, 0.92; 95% CI, 0.88-0.95; P <0.001).. Obesity and overweight are associated with lower risk of active TB. Future studies should investigate the underlying mechanisms and clinical and epidemiological consequences of these findings.

Topics: Adult; Body Mass Index; CD4-CD8 Ratio; Comorbidity; Cross-Sectional Studies; Female; Health Surveys; Humans; Leptin; Lymphocyte Activation; Male; Middle Aged; Overweight; Risk Factors; T-Lymphocytes; Taiwan; Thinness; Tuberculosis

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Macroglobulins; Biomarkers; Blood Protein Electrophoresis; Body Mass Index; Child; Child, Preschool; Comorbidity; Disease Progression; Disease Susceptibility; Electrophoresis, Polyacrylamide Gel; Ethnicity; Female; Follow-Up Studies; Haptoglobins; Humans; Immunocompromised Host; India; Infant; Interferon-gamma Release Tests; Latent Tuberculosis; Leptin; Male; Malnutrition; Middle Aged; Prospective Studies; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transferrin; Tuberculin Test; Tuberculosis; Young Adult

In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis.. Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins.. Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients.. ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis.

Topics: Adult; Biomarkers; Case-Control Studies; Diagnosis, Differential; Female; Humans; Intercellular Adhesion Molecule-1; Leptin; Male; Middle Aged; Sarcoidosis; Tuberculosis

Topics: Acquired Immunodeficiency Syndrome; Animal Rights; Compassionate Use Trials; Coronary Artery Bypass; Dietary Sucrose; Drug and Narcotic Control; Drug Carriers; Drug Industry; Global Health; Health Policy; Humans; Leptin; Lipodystrophy; Malaria; Nonprescription Drugs; Tuberculosis; World Health Organization

Tuberculosis (TB) is a infectious disease characterised by a profound immune-endocrine metabolic imbalance, including a diminution in leptin plasma levels. Leptin appears to be the link between nutritional status and the development of a protective immune response.. To examine the effects of leptin on the proliferation and production of interferon-gamma (IFN-γ) by peripheral blood mononuclear cells (PBMC) in TB patients and healthy controls stimulated with mycobacterial antigens with or without leptin. As macrophages are key cells in mycobacterial containment, the effect of leptin on the production of interleukin (IL) 1β and IL-1Ra by the monocytic cell line THP-1 was also studied.. Leptin diminished the proliferative capacity of PBMC on mycobacterial stimulation, and had no effect on IFN-γ production in terms of measurements in culture supernatants or intracytoplasmic analysis using flow cytometry. Real-time polymerase chain reaction studies of PBMC from TB patients revealed a preserved expression of leptin receptor. Furthermore, IL-1β and IL-1Ra secretion by THP-1 cells was not modified by leptin treatment.. The study results do not support the utility of treatment with leptin to correct immune imbalances due to TB.

Topics: Adult; Antigens, Bacterial; Case-Control Studies; Cell Line; Female; Humans; Immunity, Cellular; Interferon-gamma; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Leptin; Leukocytes, Mononuclear; Male; Monocytes; Mycobacterium tuberculosis; Real-Time Polymerase Chain Reaction; Tuberculosis; Young Adult

Wasting is a systemic manifestation of tuberculosis (TB) and is often thought to affect the severity and outcome of the disease. Leptin and several cytokines/proteins are thought to play a role in the relationship between TB, nutritional status and host immune response. The aim of this study was to determine the association of C-reactive protein (CRP), an inflammatory response protein and serum leptin levels with wasting in childhood TB.. A cross-sectional observational analytic study was conducted at two hospitals in West Java from January to March 2010. The subjects were 13 children aged 2-120 months who were infected with TB and 26 healthy children of the same age and gender as the comparison group. History-taking and anthropometric, physical, serum CRP and leptin examinations were conducted for each subject. The association of CRP and serum leptin levels with wasting in childhood TB was studied.. Serum leptin levels were lower (95 percent confidence interval [CI] 314.0-1,228.9 pg/mL, p-value less than 0.001) and serum CRP levels were higher (95 percent CI 16.5-81.1 mg/L) in the subjects than in the comparison group. There were positive correlations between leptin and body mass index (p-value less than 0.001) and between CRP and wasting (p-value less than 0.001), but a negative correlation between leptin and wasting (p-value less than 0.001).. Elevated serum CRP levels and a decrease in serum leptin levels are associated with an increase in wasting in childhood TB.

Topics: Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cost-Benefit Analysis; Cross-Sectional Studies; Female; Humans; Immune System; Infant; Leptin; Male; Treatment Outcome; Tuberculosis; Weight Loss

Wasting is a prominent feature in tuberculosis (TB), but its underlying mechanisms are incompletely understood. Immunoendocrine disturbances may be linked to the consumption state of TB patients, since hormones and cytokines can affect energy expenditure and metabolism. To approach this possibility, we have determined leptin, IL-18, and adrenal steroid plasma levels and body mass index (BMI) in newly diagnosed patients with mild, moderate and severe pulmonary TB, household contacts (HHC), and healthy controls (HCO). HHC displayed higher levels of leptin than HCO and TB patients. TB patients showed a gradual decrease in BMI and leptin concentrations with increasing disease severity, whereas a positive correlation between this hormone and BMI was found in the HCO group. Cortisol concentrations tended to be higher in TB patients. DHEA levels were decreased in TB patients and to a lesser extent in HHC, whereas IL-18 concentration was significantly increased in patients with severe disease. Since HHC are known to cause a latent subclinical infection, it seems clear that controlled tuberculous infection and manifested TB disease are accompanied by a dissimilar profile of immunoendocrine markers.

Topics: Adult; Biomarkers; Body Mass Index; Cachexia; Female; Humans; Hydrocortisone; Interleukin-18; Leptin; Male; Neuroimmunomodulation; Neurosecretory Systems; Steroids; Tuberculosis

Topics: Dendritic Cells; Humans; Leptin; Tuberculosis

Tuberculosis (TB) and human immunodeficiency virus (HIV) are classical wasting diseases accompanied by immunosuppression. As leptin is involved in the weight regulation and cellular immunity, we investigated the role of leptin levels in the co-infection of HIV and TB (HIV-TB).. The study group consists of the patients with asymptomatic HIV infection (n = 20), patients with HIV-TB co-infection (n = 20) and healthy control subjects (n = 20). Serum leptin levels and the concentrations of IFN-gamma, TNF-alpha, IL-12 and IL-4 cytokines were measured by ELISA before the start of the treatment. CD4+ T-cell counts were determined in patients with HIV and HIV-TB by flow cytometry. Body mass index (BMI) of the study subjects was calculated.. Serum leptin levels and BMI were significantly lower in the patients with HIV-TB than control and HIV subjects. Multivariate regression analysis showed that serum leptin concentration was significantly dependent on BMI and sex but not on age and the disease groups. The leptin levels did not correlate either with CD4+ T-cell counts or with any of the serum cytokines in HIV and HIV-TB patients.. Thus our finding suggests that the leptin concentrations were strongly associated with BMI and gender but not with the disease state or with the circulating cytokine levels.

Topics: Adult; Body Mass Index; CD4 Lymphocyte Count; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; HIV Infections; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Regression Analysis; Tuberculosis

Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease. Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein (CRP), tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls (615 vs. 2,550 ng/liter; P < 0.001). Multivariate regression analysis showed that body fat mass and inflammation were two independent factors determining plasma leptin concentrations; there was a positive correlation between fat and leptin, whereas, unexpectedly, leptin was inversely associated with CRP and tumor necrosis factor-alpha production. Concentrations of both CRP and leptin were independently associated with loss of appetite. Our results do not support the concept that weight loss in tuberculosis is caused by enhanced production of leptin. Rather, loss of body fat leads to low plasma leptin concentrations, and prolonged inflammation may further suppress leptin production. Because leptin is important for cell-mediated immunity, low leptin production during active tuberculosis may contribute to increased disease severity, especially in cachectic patients.

Topics: Adipose Tissue; Adult; Antitubercular Agents; Appetite; Body Weight; Cytokines; Female; Humans; Inflammation; Leptin; Male; Osmolar Concentration; Reference Values; Tuberculosis