Elevated serum levels of IL-8 in patients with HIV infection.

Serum levels of IL-8 were determined in HIV-infected individuals and the results were compared with those for HIV- controls. The IL-8 levels were measured by an ELISA with a MoAb and a polyclonal antibody to recombinant IL-8. The means and 95% confidence intervals of IL-8 in sera of 36 HIV-infected individuals and 32 matched controls were 275 and 216-349 pg/ml, and 8 and 4-14 pg/ml, respectively, showing a 34-fold increase in IL-8 in the circulation of HIV-infected individuals. This increase does not appear to be related to the disease state, infection or systemic medical agents. This finding suggests the possible involvement of IL-8 in the pathogenesis of HIV-induced disease.     

Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection.

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean +/- s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV- male homosexuals and 44 matched controls were 6.1 +/- 0.3 ng/ml, 4.4 +/- 0.3 ng/ml and 3.4 +/- 0.2 ng/ml, respectively. All these values were significantly different between each of the groups (P less than 0.001-0.05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-alpha was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-alpha/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.     

Basic fibroblast growth factor: serum levels in the female

This study investigated serum levels of basic fibroblast growth factor (b FGF), a potent angiogenic factor, during distinct periods of the female life and compared them with corresponding levels in age-matched males. Healthy females (n = 59) and males (n = 53) were included in the study, divided into six groups: fetuses (cord blood), neonates, children, adults (females in proliferative and secretory phase), pregnant and "elderly" men and women. Serum b FGF levels were measured by an enzyme immunoassay. No statistically significant difference was found between both genders. Blood levels in fetuses and neonates were significantly increased as compared to adults (p = 0.01, p = 0.02, respectively). Restricting the analysis to females, all age groups, but fetuses (p = 0.05), demonstrated no difference when compared to proliferative phase adults. In conclusion, b FGF serum levels do not differ between males and females and are elevated in fetal and neonatal life, when growth and development are enhanced.     

Increased levels of circulating fibroblast growth factor 21 in children with Kawasaki disease

Clinical and Experimental Medicine - The purpose of this study was to examine the serum levels of fibroblast growth factor 21 (FGF21) in children with acute Kawasaki disease (KD) and to investigate...     

Increased levels of immunological markers in the respiratory tract but not in serum correlate with active pulmonary mycobacterial infection in mice

Immunological tests for the diagnosis of tuberculosis (TB) have relied mostly on detection of immune markers in serum or release of cytokines by mononuclear cells in vitro . These tests, although useful, sometimes fail to discriminate between active infection and contact with mycobacteria or vaccination. TB is primarily a disease of the lung, and therefore identification of immunological markers in the respiratory tract will be more likely to reflect the infection status or disease activity. In this study, it is demonstrated that active infection of mice with Mycobacterium bovis bacille Calmette-Guérin (BCG), but not exposure to heat-killed BCG, induced production of interleukin-12 (IL-12), interferon-γ (IFN-γ) or soluble tumour necrosis factor receptors (sTNFRs) locally in the lungs, as detected in bronchoalveolar lavage (BAL) fluid. There was a strong correlation between bacterial growth in the lung and levels of sTNFRs, and to some extent IL-12 and IFN-γ, in BAL fluid. Furthermore, sTNFR levels increased significantly in BAL fluid after reactivation of controlled infection with dexamethasone, and this correlated with increased bacterial growth in the lungs. Finally, infection, but not exposure to non-replicating mycobacteria, induced specific IgG and IgA in BAL fluid. Elevated levels of all biomarkers measured were also detected in the serum, but correlation with infection was not as clear as in the case of BAL fluid. Taken together, the detection of sTNFRs and mycobacterium-specific antibodies, especially IgA, locally in the lungs could be used as immunological markers for the diagnosis of TB.     

Circulating fibroblast growth factor 21 in patients with liver cirrhosis

Fibroblast growth factor 21 (FGF21) is an adipokine and hepatokine, and its hepatic expression is induced in the injured liver. Adiponectin, whose systemic levels are positively correlated with measures of hepatic injury in patients with liver cirrhosis, is a downstream effector of FGF21. The aim of the present study was to identify possible associations of serum FGF21 with measures of liver function in patients with liver cirrhosis. FGF21 was determined by ELISA in serum of 42 patients. FGF21 was not linked to disease severity assessed by the Child–Pugh and MELD score. Levels were not changed in those patients with varices and/or ascites. Systemic FGF21 did not correlate with markers of liver and kidney function, inflammatory proteins or adipokines like adiponectin. Levels in hepatic and portal vein of 37 patients were also measured, but there was no transhepatic FGF21 gradient. Three months after insertion of a transjugular intrahepatic shunt hepatic venous pressure gradient was markedly improved, while FGF21 in serum of these 13 patients was not changed. The present study shows that hepatic release and systemic FGF21 are not linked to measures of liver function in patients with liver cirrhosis.     

High vascular endothelial growth factor levels in NZW mice do not correlate with collagen deposition in allergic asthma

BACKGROUND: Eosinophils contribute to the early features of allergic lung inflammation through the generation and release of a plethora of mediators. Eosinophil peroxidase (EPO) is one of the eosinophil granule proteins involved in the early response, but its participation in airway remodeling is not established. The present study addressed this question comparing an EPO-deficient mouse strain (NZW) with BALB/c and C57Bl/c strains. METHODS: Mice were immunized with ovalbumin/alum, challenged twice with ovalbumin aerosol, and lung responses were measured at day 22 or 28. Collagen, mucus and eosinophils were determined in lung sections stained with picrosirius, periodic acid-Schiff or hematoxylin-eosin; transforming growth factor-beta and vascular endothelial growth factor were determined by ELISA, lipid bodies by enumeration in osmium-stained eosinophils, and airway reactivity to methacholine in isolated lung preparations. RESULTS: NZW mice showed significantly less collagen around bronchi and blood vessels, less mucus and less eosinophils around bronchi. Eosinophil lipid body formation and airway hyperreactivity were comparable among strains. Levels of transforming growth factor-beta were also comparable; however, the NZW mice showed much higher levels of vascular endothelial growth factor, even under basal conditions. CONCLUSIONS: In allergic lung inflammation, the combination of EPO deficiency and overexpression of VEGF found in NZW mice is associated with less collagen deposition, less mucus and reduced tissue eosinophilia. Eosinophil activation and airway hyperreactivity in NZW mice were similar to the other strains.     

Elevated serum levels of vascular endothelial growth factor are associated with tumor-associated macrophages in primary breast cancer

We analyzed serum and tumor samples from 133 patients with operable primary breast cancer to determine the possible relationship between presurgery and postsurgery circulating serum vascular endothelial growth factor (VEGF) levels and tumor-associated macrophage (TAM) numbers, tumor VEGF expression, and other immunohistochemical parameters. A significant positive correlation was observed between the number of TAM and postsurgery circulating VEGF values (P < .05). Moreover, patients with a p53+ tumor had higher postsurgery serum VEGF levels than those with a p53- tumor (P < .05), and tumor p53 overexpression correlated significantly with TAM number (P = .007). We observed no significant association between serum values and tumor VEGF expression. Although the macrophage index was higher in VEGF+ than in VEGF- tumors, the differences were not statistically significant. Our data show a positive interrelation between high circulating VEGF levels, the number of TAM, and p53 overexpression, a relationship that might have an important role in the enhanced angiogenesis processes in breast cancer.     

Elevated levels of serum macrophage migration inhibitory factor in patients with pulmonary tuberculosis

Macrophage migration inhibitory factor (MIF) was originally described as a T-cell-derived cytokine that inhibits the random migration of macrophages and promotes the delayed-type hypersensitivity reaction. MIF plays an important role in the regulation of the Th1/Th2 balance in inflammatory response. This study investigated serum levels of circulating MIF in patients with pulmonary tuberculosis. The levels of MIF in sera were measured by enzyme-linked immunosorbent assay in 34 patients with pulmonary tuberculosis (16 males and 18 females) and 30 healthy controls (15 males and 15 females). The mean levels of circulating MIF values were significantly higher in those with pulmonary tuberculosis (19.84 +/- 11.27 ng/ml; P < 0.0001) than in the healthy controls (4.38 +/- 1.34 ng/ml). Circulating MIF values significantly correlated with circulating interferon-gamma values (r = 0.537, P < 0.0001). Thus, MIF may play an important role in immune responses to human infection with Mycobacterium tuberculosis.     

Elevated serum levels of CCL17 correlate with increased peripheral blood platelet count in patients with active tuberculosis in China

The serum levels of Th2 markers, including CCL17 (thymus and activation-regulated chemokine [TARC]), CCL22 (macrophage-derived chemokine [MDC]), and soluble CD30, were measured in 101 HIV-negative tuberculosis patients, 103 healthy community controls, and 18 tuberculosis patients in recovery. The levels of CCL17/TARC (249.8 ± 19.91 versus 143.9 ± 10.54, P < 0.0001) and sCD30 (7.78 ± 0.44 versus 4.93 ± 0.23, P < 0.0001) were significantly higher in patients with active tuberculosis than in controls; however, the CCL22/MDC serum level had no statistical difference between the groups (579.9 ± 16.42 versus 556.5 ± 15.29, P = 0.298). The counts of platelet and eosinophil in the peripheral blood of patients with active tuberculosis are significantly increased as well (289.4 ± 8.14 versus 248.3 ± 5.34 [P < 0.0001] and 165.1 ± 14.33 versus 102.5 ± 10.72 [P = 0.0005], respectively), and the platelet counts were positively correlated with serum TARC levels (Pearson r = 0.456, P < 0.0001), which indicates a new source of Th2 bias showing in active TB patients.     

Serum IgA levels induced by rotavirus natural infection, but not following immunization with the RRV-TV vaccine (Rotashield), correlate with protection

To directly compare serum rotavirus specific IgA as a marker of protection in children vaccinated with the RRV-TV (Rotashield) vaccine and in naturally infected children, we studied pre-existing rotavirus IgA antibodies by ELISA assays in these groups of children within the first 5 days after the onset of a diarrhea episode, due or not to rotavirus. In immunized children, rotavirus IgA titers were similar between infected and non-RV infected children. In non-immunized children, the proportion with rotavirus IgA titers was significantly greater in non-RV infected children (58%) than in infected children (31%). Additionally, a titer >/=1:800 was associated with 68% protection. Thus, in this study serum rotavirus IgA showed a good correlation with protection in children pre-exposed to natural infection but not in those immunized with the RRV-TV vaccine.     

Levels of hepatocyte growth factor in serum correlate with quality of life in hemodialysis patients

Purpose: Patients with end stage renal failure (ESRD) report low quality of life and inflammation may be one of the contributing factors. We studied if the hemodialysis induced inflammation correlates with the patients quality of life. Methods: Study was performed in 76 (35 males and 41 females) ESRD patients treated with hemodialysis. Effect of one dialysis session on blood concentration of Vascular Endothelial Growth Factor (VEGF), Hepatocyte Growth Factor (HGF), Interleukin 6 (IL6) and Monocyte Chemoattractant Protein-1 (MCP-1) was studied. Results were correlated with answers given by patients to a short questionnaire composed of questions from Kidney Disease Quality of Life Short Form (KDQoL-SF) questionnaire. Results: Hemodialysis induced increase of serum level of HGF (+117%) and IL-6 (+17%). Declared by patients health status correlated with their age, GFR, kt/V and hemodialysis induced change in serum IL6 and HGF level (R² = 0469, P < 0.001). Physical activity correlated with age, serum IL-6 and hemodialysis induced change in serum HGF and VEGF (R² = 0.362, P < 0.001). Presence of social/mental problems during previous 4 weeks correlated with age, serum HGF and hemodialysis induced changes in serum HGF and VEGF levels (R² = 0.333, P < 0.001). Interference of the kidney disease with daily life activities correlated with age, serum VEGF and hemodialysis induced change in serum HGF and IL6 levels (R² = 0.422, P < 0.001). Conclusion: Inflammation correlates with reduced quality of life in ESRD. Low hemodialysis-induced release of the anti-inflammatory cytokine HGF correlates with impaired quality of life in that group of patients.     

Correlation between viral RNA levels but not immune responses in plasma and tissues of macaques with long-standing SIVmac251 infection

Plasma virus in human immunodeficiency virus type 1/simian immunodeficiency virus (HIV-1/SIV) infection most likely results from the combination of viruses produced in different tissues. As immunological pressure may be higher in effector sites than secondary lymphoid tissues, we investigated quantitative and qualitative changes in viral RNA in blood and tissues of 10 Mamu-A*01-positive SIV-infected macaques in parallel with the frequency of CD8+ T cells recognizing the dominant Gag181-189 CM9 epitope. The plasma virus level in these macaques directly correlated with the viral RNA levels in lymph nodes, spleen, lungs, colon, and jejunum. In contrast, the frequency of the Gag181-189 CM9 tetramer did not correlate with SIV RNA levels in any compartment. We investigated the presence of viral immune escape in RNA from several tissues. The complete substitution of wild-type genotype with viral immune-escape variant within the Gag181-189 CM9 epitope was associated with low tetramer response in all tissues and blood of two macaques. In one macaque, the replacement of wild type with an immune-escape mutant was asynchronous. While the mutant virus was prevalent in blood and effector tissues (lungs, jejunum, and colon), secondary lymphoid organs such as spleen and lymph nodes still retained 80% and 40%, respectively, of the wild-type virus. These results may imply that there are differences in the immunological pressure exerted by cytotoxic T lymphocytes (CTLs) in tissue compartments of SIVmac251-infected macaques.     

Urine fibroblast growth factor 23 levels in hypertensive children and adolescents

AimTo determine the correlation of urinary fibroblast growth factor 23 (FGF23) excretion with blood pressure and calcium-phosphorus metabolism.MethodsThe study included 42 hypertensive (17 girls) and 46 healthy children and adolescents (17 girls) aged 6-18 years admitted to the Department of Pediatrics and Nephrology, Medical University of Białystok between January 2013 and December 2013. FGF23 in urine was measured using Human Intact FGF-23 ELISA Kit.ResultsHypertensive participants had significantly higher urine FGF23/creatinine values than the reference group (8.65 vs 5.59 RU/mg creatinine, P = 0.007). Urine FGF23/creatinine positively correlated with systolic blood pressure in all participants. In hypertensive patients, urine FGF23/creatinine positively correlated with serum calcium and negatively with serum 25(OH)D, urinary calcium, phosphorus, and magnesium.ConclusionThis study found that FGF23 may play an important role in the pathogenesis of hypertension in children and adolescents, but our results should be confirmed by further studies.Hypertension is a chronic medical condition and a major risk factor for cardiovascular disease, heart failure, and chronic kidney disease (CKD). Hypertension was found to be associated with several factors, among them calcium-phosphorus imbalance, lack of vitamin D, and serum parathyroid hormone (PTH) (1-5). However, far too little attention has been paid to phosphates and hormonal mechanisms responsible for their regulation, especially since the consumption of phosphorus has considerably increased in recent years. Some studies have shown that serum phosphorus increases BP (11,12). However, recent studies have found that high phosphorus intake reduces BP, when the diet is rich in calcium (6-8), while other have shown that BP was reduced by low phosphorus and high calcium diet (9,10).Phosphate concentration is primarily regulated by PTH and fibroblast growth factor 23 (FGF 23) – phosphatonin, produced by osteoblasts/osteocytes in the bone, which, similarly to PTH, stimulates phosphaturia. FGF23 decreases renal calcitriol production and inhibits PTH secretion. Its main function is to maintain phosphate homeostasis by increasing urinary phosphate excretion and decreasing serum 1,25(OH)₂D (13,14) In patients with CKD, it positively correlated with PTH secretion (15,16). The increase in FGF23 in those patients led to an early development of secondary hypertension by suppression of 1,25(OH)₂D production (17), and low phosphate intake of phosphorus binders caused 35% decrease in plasma FGF23 level (18). However in healthy individuals no changes in FGF23 levels were observed after both phosphate deprivation and loading (19,20).FGF 23 is also involved in renal sodium handling (21) and, what is even more interesting, it suppresses the expression of angiotensin-converting enzyme-2 (ACE2) in CKD-mice and thereby activates renin-angiotensin-aldosterone system (RAAS) (22). FGF23 can also influence the RAAS indirectly through vitamin D (23), which probably reduces renin gene expression and secretory activity of the juxtaglomerular apparatus, the main place of production of renin (24).The investigation of the effect of FGF23 on hypertension is not confined to in vitro models. Hypertensive people were found to have significantly higher plasma FGF23 level than normotensive people (25). FGF23 was shown to have an association with markers of inflammation in individuals with CKD stages 2-4 (26), and with impaired endothelium-dependent vasodilatation in healthy individuals and early CKD patients (27). This effect of FGF23 might also result indirectly from a decrease in 1,25 (OH)₂D (28). FGF23 also correlated with asymmetrical dimethylarginin (ADMA), which is an endogenous inhibitor of NO synthase and a biomarker of endothelial dysfunction (29).So far, however, the relevance of FGF23 in primary arterial hypertension has been under-investigated. What is more, available data focus on adult hypertensive patients and possible relation of phosphorus intake and increased FGF23 concentration to elevated BP (25). There is a paucity of similar data in children and adolescents. The aims of this research were to determine whether urinary excretion of FGF23 in hypertensive children and adolescents was higher than in healthy controls and whether its urinary level correlated with serum calcium, phosphorus, vitamin D, and PTH concentrations. Reference group data were obtained from the OLAF study, which established the reference blood pressure range for Polish children and adolescents. A strong correlation between serum and urine FGF23 was previously confirmed (r = 0.92, P < 0.001) (30).     

Serial measurement of serum basic fibroblast growth factor in patients with acute cerebral infarction

Basic fibroblast growth factor (bFGF) has been reported to be involved in the pathophysiological changes following cerebral infarction. Basic fibroblast growth factor is upregulated in the brain and conduces to neuroprotection and angiogenesis in experimental brain ischemia, but the change of serum bFGF in cerebral infarction patients has not been reported. In the present study, we investigated the dynamic changes of serum bFGF in 30 patients with acute cerebral infarction and found that serum bFGF increased significantly after cerebral infarction compared with the control group (p<0.05). Serum bFGF peaked on day 3 (15.46 +/- 5.58 pg/ml; p<0.01) and remained significantly elevated on day 14 following cerebral infarction. In this study, it was also found that the levels of bFGF with large infarction were higher at each time point than those with moderate or small infarction (p<0.05). There was a positive correlation between the peak level of bFGF and improvement of clinical neurological deficits scored by Scandinavian Stroke Scale (SSS) (r=0.596; p<0.05). These results suggest that the serum bFGF level increased significantly after cerebral infarction and the level of serum bFGF could be of value to estimate the infarction size and clinical prognosis.     

Elevated serum D-arabinitol levels in patients with sarcoidosis.

D-Arabinitol has been found in the serum of patients with candidiasis in an incidence varying from 38 to 82%. While screening serum by gas chromatography for the presence of this sugar, we observed elevated concentrations in several patients with sarcoidosis. In an attempt to determine the significance of this chance observation, we tested serum from additional patients with sarcoidosis along with serum from patients with other clinical conditions known to be associated with elevated D-arabinitol levels. Of 53 patients with sarcoidosis, 27 (51%) had elevated concentrations of this compound. Only one of these patients had decreased renal function (creatinine, 2.5 mg/dl). We were unable to correlate elevated values with extent of the disease. Although the significance of this finding is not clear, it may represent a clue to the pathogenesis of sarcoidosis.