Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B

PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis.

Expression of FAS protein [CD95] and fas ligand in liver tissue of patients with HCV-induced chronic liver disease and its correlation with the disease progression

This study evaluated hepatic expression of both Fas and Fas ligand [FasL] in patients with hepatitis c virus [HCV]-induced chronic liver disease and its correlation with the histopathological activity and laboratory parameters as an early predictor of advancement of the disease. The selected patients were [39] males and [21] females, their ages ranged from [20-67years] with a mean of 43.5 +/- 4.5 years, as well as [10] subjects [normal individuals] serving as a control group. They were [7] males and [3] females, their age ranged from [26-53 years] with a mean of 39.5 +/- 7.3 years. Patients were grouped as [1] Chronic hepatitis [CH] group including [30] patients with chronic viral hepatitis C. [2] Liver cirrhosis [LC] group including [30] patients with post hepatitis C cirrhosis. Liver biopsy was done for all subjects using an automated 18-gauge true cut needle. Sections were stained with Haematoxylin and Eosin for histopathological diagnosis and with Maisson and Trichrome for assessment of fibrosis. Unstained paraffin sections from each case were subjected for immuno-histochemical procedures using indirect immunoflourescence technique for detection of apoptotic hepatic and lymphocytic cells using monoclonal antibodies. Semiquantitative analysis of the pattern and distribution of the Fas antigen and Fas Ligand as indicators for hepatic apoptosis was studied and assessed

High concentration of serum soluble fas in patients with head and neck carcinoma: a comparative study before and after surgical removal of tumor

Alternative splicing of the Fas transcript can produce a natural secreted isoform of this molecule. Some cancer cells can also produce soluble Fas [sFas] which may have suppressive effects on the immune system's anti-tumor response. Elevated concentrations of sFas have been detected in the sera of patients with different malignancies. The concentrations of sFas in sera of patients with head and neck carcinoma [HNC, n=98] and healthy individuals [n=30] were measured by Sandwich ELISA and compared to values obtained six months after surgical removal of the tumor [n=48]. Data were correlated with different clinical findings of the patients. sFas concentrations in the sera of HNC patients were found to be significantly higher in patients with different tumor stages. sFas concentration did not correlate with age or tumor invasiveness, however a higher concentration of sFas was found in the sera of patients who had higher tumor grades. Surgical removal of tumors in patients resulted in a substantial decrease in sFas concentration. The initial rise in sFas concentration in the sera of HNC patients and its consequent decrease could be regarded as a sign of tumor suppressive mechanisms. Additional studies are needed to fully elucidate this mechanism however these findings might show the prospective use of such biomarkers to determine disease prognosis and even immunotherapeutic applications

Soluble form of fasl [sFasL] in adult asthma

sFasL is the soluble form of FasL inducing apoptosis by binding to Fas. Fas/sFasL could be the most important mechanisms in inflammatory conditions such as asthma by controlling inflammatory responses. This study was undertaken to determine the level of sFasL in allergic and non- allergic asthmatic patients with different stages of asthma control. Twenty asthmatic patients were enrolled and divided into controlled and uncontrolled patient groups. They were divided into 4 subgroups including controlled/allergic, controlled/non-allergic, uncontrolled/allergic and uncontrolled/non-allergic subgroups. Five normal subjects were selected as a control group. From all subjects, 3 ml of blood was obtained and sFasL and IgE serum levels were evaluated by a specific ELISA kit. sFasL in the controlled and uncontrolled patient groups did not have any significant difference; but in the uncontrolled/allergic subgroup, it was significantly lower than that in the control group and also higher in the uncontrolled/non-allergic subgroup insignificantly. In patients with acute inflammatory conditions, sFasL had an increasing effect to control inflammation observed in uncontrolled/non-allergic subgroup, but unexpectedly not in the uncontrolled/allergic subgroup. Probably in allergic patients, there are factors or mechanisms that inhibit sFasL production or expression

Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals.

BACKGROUND & OBJECTIVES: Apoptosis causes a decline in the counts of uninfected bystander CD4+ T cells in HIV infection. The rate of disease progression of HIV infection is considered to be faster in the developing countries. The present study was carried out to investigate certain markers for apoptosis in immunopathogensis of disease in HIV infected south Indian population. METHODS: Soluble Fas (sFas) antigen and Fas ligand levels in plasma samples from 39 antiretroviral treatment naïve patients was estimated and compared with T cell subsets and HIV-1 viral load. RESULTS: The mean sFas antigen levels among controls and the CDC A, B and C clinical stages were 2.77, 3.08, 3.26 and 3.28 ng /ml respectively, higher though not significantly among HIV-1 infected individuals compared to controls. The mean sFas ligand levels in CDC A, B and C stages were 0.138, 0.125 and 0.117 ng/ml respectively were higher (P<0.001) than controls (0.073 ng/ml) and positively correlated with total lymphocyte % (r=0.43, P =0.007). sFas antigen levels were negatively correlated with total WBC count (r=-0.34, P=0.04), CD4% (r=-0.4, P=0.01) and CD4:CD8 ratio (r=-0.37, P=0.02). There was an increase in plasma levels of sFas antigen and Fas ligand over time in asymptomatics. INTERPRETATION & CONCLUSION: The high levels of sFas antigen and Fas ligand seen in HIV infected individuals suggest increased activation and apoptosis of T cells, due to constant stimulation of the immune system by inter-current infections of HIV infected individuals in south India.

Inflammation markers in healthy and periodontitis patients: a preliminary data screening

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.

Avanços no diagnóstico da doença periodontal levam a métodos nos quais o risco e atividade da doença periodontal podem ser identificados e quantificados por biomarcadores. Pacientes com periodontite podem apresentar elevados níveis circulatórios de marcadores inflamatórios específicos que podem ser correlacionados com a severidade da doença. Portanto, o objetivo desse estudo foi avaliar as diferenças nos níveis séricos de biomarcadores inflamatórios em pacientes saudáveis e com doença periodontal. Foram incluídos no estudo 25 pacientes (8 saudáveis e 17 com periodontite crônica). Uma amostra de 15 mL de sangue foi obtida para identificar os marcadores inflamatórios simultaneamente utilizando Array de proteínas através de citometria de fluxo. De 24 citocinas inflamatórias analisadas, apenas 3 (RANTES, MIG e Eotaxina) apresentaram diferenças estatisticamente significantes (p<0,05) entre os dois grupos. Conclui-se que alguns marcadores inflamatórios selecionados apresentam diferença de concentração em pacientes com periodontite e saudáveis. A análise do perfil de citocinas pode ser utilizada tanto para distinguir pacientes periodontais de pacientes saudáveis, como para medir o risco à doença. Contudo, mais estudos com número maior de amostras são necessários para validar os achados sobre os biomarcadores específicos.

Changes in serum levels of soluble interleukin-2 receptor and fas-ligand expression in relation to disease activity of systemic lupus erythematosus

Serum soluble IL-2 receptors [sIL2R] levels and Fas-ligand [Fas-L] expression on peripheral blood mononuclear cells [PBMC] were determined in patients with Systemic Lupus Erythematosus [SLE] to assess whether there was any relationship between them and disease activity. Enzyme Linked Immunosorbant assay [ELISA] technique was done on serum samples collected from 36 SLE patients and 25 healthy controls for determination of sIL2R level. RT-PCR was done also on PBMC samples collected from the same patients and controls for detection ofFas-L mRNA. We found significant increase of sIL2R in the SLE group [327.6 +/- 73.5 pg/ml] compared to healthy controls [119.7 _ 12.6 pg/ml] [p<0.001]. Levels of sIL2R were found to correlate significantly with clinical manifestation and serological markers of active SLE: fatigue [p<0.05], renal involvement [p<0.01], pulmonary involvement [p<0.05], high levels ofanti-ds DNA antibody [p<0.001] and high C3 level [p<0.0001]. Fas-L mRNA was expressed in PBMC from [88.9%] SLE patients and not detected in healthy controls. Fas-L positive SLE patients correlate significantly with clinical manifestation and serological markers of active SLE: fatigue [p<0.0001], rash [p<0.05], renal affection [p<0.001], high levels ofanti-ds DNA antibody [p<0.0001] and high C3 level [p<0.0001]. Levels ofsIL2R and Fas-L expression correlate significantly with disease activity [p<0.001, 0.001, 0.05, 0.005, respectively]. these findings indicate that sIL2R represent a new early useful serological marker to monitor disease activity in SLE patients. Fas-L expression increased in SLE patients, this increasing was in parallel to disease activity, so it is used as late marker to monitor the severity of the disease

Apoptosis in type 2 diabetic patients with micro vascular complications

Type 2 diabetes mellitus results from an inadequate adaptation of the functional pancreatic beta cell mass in the face of insulin resistance. Apoptosis is programmed cell death or cell suicide, it is an energy-requiring process that involves de novo protein synthesis. Apoptotic mechanisms could explain insulin deficiency through a reduction in absolute beta cell mass. This study was conducted on 49 patients with type 2 diabetes mellitus from Internal Medicine Department, Kasr- El Aini hospital. They were classified into group A [10 patients] without micro vascular complications, group B [39 patients]with micro vascular complication [peripheral neuropathy, retinopathy and nephropathy] and 10 healthy persons served as control group[group C].All subjects were subjected to full Clinical assessment and routine laboratory investigations, 24 hours urinary albumin, ECG, fundus examination and quantitative assay of proapoptotic markers [Fas, FasL, and Bcl2 proteins] There was significant correlation behveen fasting blood glucose and Fas, FasL, and Bcl2 [P value