C-X-C motif chemokine 10 (CXCL10) also known as interferon γ-induced protein 10 kDa (IP-10) or small-inducible cytokine B10 is a cytokine belonging to the CXC chemokine family. CXCL10 binds CXCR3 receptor to induce chemotaxis, apoptosis, cell growth and angiostasis. Alterations in CXCL10 expression levels have been associated with inflammatory diseases including infectious diseases, immune dysfunction and tumor development. CXCL10 is also recognized as a biomarker that predicts severity of various diseases. A review of the emerging role of CXCL10 in pathogenesis of infectious diseases revealed diverse roles of CXCL10 in disease initiation and progression. The potential utilization of CXCL10 as a therapeutic target for infectious diseases is discussed.

ObjectiveThe purpose of this study was to quantitate the derangements in intermediary carbohydrate metabolism and oxygen use in severely septic patients in comparison with healthy volunteers. Summary Background DataIt commonly has been assumed that the development of lactic acidosis during sepsis results from a deficit in tissue oxygen availability. Dichloroacetate (DCA), which is known to increase pyruvate oxidation but only when tissue oxygen is available, provides a means to assess the role of hypoxia in lactate production. MethodsStable isotope tracer methodology and indirect calorimetry was used to determine the rates of intermediary carbohydrate metabolism and oxygen use in five severely septic patients with lactic acidosis and six healthy volunteers before and after administration of DCA. ResultsOxygen consumption and the rates of glucose and pyruvate production and oxidation were substantially greater (p < 0.05) in the septic patient compared with healthy volunteers. Administration of DCA resulted in a further increase in oxygen consumption and the percentage of glucose and pyruvate directed toward oxidation. Dichloroacetate also decreased glucose and pyruvate production, with a corresponding decrease in plasma lactate concentration. ConclusionsThese findings clearly indicate that the accumulation of lactate during sepsis is not the result of limitations in tissue oxygenation, but is a sequelae to the markedly increased rate of pyruvate production. Furthermore, the substantially higher rate of pyruvate oxidation in the septic patients refutes the notion of a sepsis-induced impairment in pyruvate dehydrogenase activity. 97

The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature.Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.

A new stable isotope method for the determination of substrate oxidation rates in vivo is described and compared with indirect calorimetry at rest and during high-intensity exercise (30 min at 80-85% maximal O2 uptake capacity) in six well-trained cyclists. This method uses the absolute ratios of 13C/12C in expired air, endogenous glucose, fat, and protein in addition to O2 consumption and is independent of CO2 production (VCO2). Carbohydrate and fat oxidation rates at rest, calculated by both methods, were not significantly different. During exercise the breath 13C/12C ratio increased and reached a steady state after 15-20 min. Carbohydrate oxidation rates during exercise were 39.4 +/- 5.2 and 41.7 +/- 5.7 mg.kg-1.min-1 [not significant (NS)], and fat oxidation rates were 7.3 +/- 1.3 and 6.9 +/- 1.2 mg.kg-1.min-1 (NS), using indirect calorimetry, and the breath ratio method, respectively. We conclude that the breath 13C/12C ratio method can be used to calculate substrate oxidation under different conditions, such as the basal state and exercise. In addition, the results obtained by this new method support the validity of the underlying assumption that indirect calorimetry regards VCO2 as a reflection of tissue CO2 production, during exercise in trained subjects, even up to 80-85% maximal O2 uptake.

Sickle cell anemia (HbSS) includes chronic inflammation, but the origin is unclear. We hypothesized that in stable HbSS patients the inflammation was associated with hypermetabolism. We compared selected hypermetabolic and key immunomodulator indicators in HbSS versus control children and examined associations between measures of hypermetabolism and inflammation. Twelve fasting asymptomatic HbSS children 6-12 years and 9 controls matched for age, gender and fat mass (FM) were studied. Proportional reticulocyte count (retic%) and resting energy expenditure (REE) represented hypermetabolism, and C-reactive protein (CRP) indicated inflammation. Proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), chemokine monocyte chemoattractant protein-1 (MCP-1), and energy balance cytokine leptin were measured. Methods were indirect calorimetry, enzyme-linked immunosorbent assay, and radioimmunoassay. Statistical analysis included simple correlation and regression analysis. REE (51 ± 6 vs. 43 ± 12 kcal/kg per fat-free mass (FFM), mean ± SD), retic% (12 ± 4 vs. 0.7 ± 0.3%), CRP (5 ± 3 vs. 0.3 ± 0.4 mg/liter), and IL-6 (71 ± 40 vs. 20 ± 7 pg/ml) were significantly higher for HbSS than controls (P < 0.05). Conversely, leptin (0.1 ± 0.1 vs. 2 ± 1 µg/liter per kgFM) and MCP-1 (34 ± 5 vs. 41 ± 4 pg/ml) were significantly lower for the HbSS subjects (P < 0.01). TNF-α was not significantly different. There were no significant associations between REE or retic% and any cytokine measured. However, CRP was significantly associated with REE in HbSS (r = 0.8, P = 0.003) and an important predictor of REE/FFM. We provide new evidence for low circulating levels of inflammatory chemokine MCP-1 in stable HbSS children, confirm mostly low cytokine levels, inflammation, and hypermetabolism and demonstrate association of hypermetabolism with inflammation via CRP but not via cytokines.