Role of intestinal microflora [Lactobadllus Acidophilus] in phagocytic function of leukocytes in type 2 diabetic patients

The prevalence of obesity, insulin resistance and type 2 diabetes has steadily increased in the last decades. In addition to the genetic and environmental factors, gut microbiota may play an important role in the modulation of intermediary phenotypes leading to metabolic disease. Infection is an important cause of morbidity and mortality in diabetic patients. Chronic hyperglycemia impairs host defense mechanism such as cell mediated immunity, polymorphonuclear leukocyte function, and antibody formation. So we aimed to study the association between intestinal microflora [Lactobacilles acidophilus] count and phagocytic activity of polymorphonuclear leukocytes in humans with type 2 diabetes. The study included 20 type 2 diabetic patients with good glycemic control and 20 type 2 diabetic patients with poor glycemic control. In addition, 20 normal healthy subjects were included as normal controls. The fecal composition of L. acidophilus was detected using de Man Rogosa Sharp agar followed by further confirmation using the polymerase chain reaction technique. Phagocytic function of polymorphonuclear leukocytes was assessed using the phagocytosis index%. Fecal L. acidophilus count was significantly increased among uncontrolled diabetic patients, while the phagocytosis index% was significantly reduced among the same patients. In uncontrolled diabetics, a significant positive correlation was observed between fecal L. acidophilus count and HbA1c and a significant negative correlation between phagocytic activity and L. acidophilus count. In conclusion, type 2 diabetes is associated with compositional changes in fecal L. acidophilus especially in the uncontrolled diabetes. The levels of glucose tolerance or severity of diabetes should be considered while linking the level of intestinal microbiota with a phagocytosis index of leukocytes

CXCR3 and CXCR4 receptors expression on peripheral blood T-lymphocytes from patients with rheumatoid arthritis

Rheumatoid arthritis [RA] is a chronic inflammatory condition that affects multiple joints. Chemokines and their receptors are involved together in the development and perpetuation of inflammation Chemokine receptors CXCR3 and CXCR4 are among the main regulators of T cell recruitment in autoimmune diseases. The present study aimed at detection of the frequency of CXCR3 and CXCR4 chemokine receptors expression on peripheral blood T-lymphocytes in patients with rheumatoid arthritis in an attempt to identify suitable targets for therapeutic intervention. Twenty eight patients with rheumatoid arthritis, selected from those attending the Rheumatology and Rehabilitation outpatient clinic, Ain Shams University Hospitals, were studied. Ten age and sex matched healthy subjects were served as controls. All patients were subjected to full medical history, thorough clinical examination, evaluation of the disease activity using disease activity score 28 [DAS28] and radiological assessment by plain X rays of both hands and feet [posterior - antero views] for the erosive changes. Peripheral blood lymphocytes analysis was performed by flow cytometry using anti-CD3, anti-CXCR3 and anti-CXCR4 monoclonal antibodies. High statistically significant difference was determined between patients and controls as regard relative count of T- lymphocytes expressing CXCR4 receptors [35.068 +/- 5.098, 23.59 +/- 4.601, respectively and P< 0.001]. Also, there was a significant positive correlation between relative count of T- lymphocytes expressing CXCR4 receptors and disease activity using disease activity sore 28 [DAS28] disease duration and the hemoglobin level. On the other hand, no significant correlation was determined between relative count of T- lymphocytes expressing CXCR3 receptors and any of the clinical and laboratory parameters of patients. Increased expression of CXCR4 on peripheral T cells of Patients [RA Patients] and its positive correlation with the disease activity indicate that this chemokine receptor plays a central role in the process of chronic inflammation in RA and suggests that targeting CXCR4 could provide a new treatment for this disease. Although our data did not prove that CXCR3 expression is higher in patients with RA, however, it can be expected that it is involved in the inflammatory process based on reported functional studies

Study of interlukin-18 in viral hepatitis C patients with chronic hepatitis and hepatocellular carcinoma

Hepatitis C virus [HCV] infection represents a serious threat to human health; often resulting in liver cirrhosis and hepatocellular carcinoma [HCC]. The exact mechanisms responsible for persistent infection and long -term hepatocellular injury are poorly understood. It is hypothesized that the pro-inflammatory cytokine IL-18 may have an important role in chronic cellular immune response towards hepatocytes in the course of the disease. Of this study was to evaluate the significance of measuring IL-18 mRNA in peripheral blood mononuclear cells [PBMCs] in viral hepatitis C patients with chronic infection and HCC. Forty selected patients with chronic HCV infection [12 with compensated liver functions "group I" ; 12 with decompensated liver functions "group II"; and 16 with HCC on top of chronic HCV infection "group III"] and 10 healthy controls with matched ages and sex were studied. Using reverse- transcriptase polymerase chain reaction [RT-PCR], detection of HCVRNA in blood of patients and quantitation of IL-18 mRNA transcripts in PBMCs of patients and control were performed. This study showed a significant increase [p<0.001] in the mean value of transcriptional expression of IL-18 gene [as a ratio to that of beta-globin] in PBMCs in all patients groups compared to control. A positive [however insignificant] correlation was detected between transcriptional expression of IL-18 gene and serum albumin [r=0.446]; ALT[r=0.074] as well as prothrombin time [r=0.332] in chronic viral hepatitis patient groups [compensated and decompensated]. A significant positive correlation was found between transcriptional expression of IL-18 gene and hepatitis C viral load in all patient groups[r=0.756; 0.669; and 0.956 respectively]. These results support the hypothesis that IL-18 has an important role in the immunopathogenetic events leading to liver injury in chronic HCV infection. The antiviral action of IL-18 might be counteracted by multiple factors leading to persistent HCV infection [as IL-10]. The question becomes important whether and to what extent the HCC is influenced by IL-18. Future follow- up studies are recommended to investigate the role of monoclonal antibody to IL-18 in amelioration of liver damage and cirrhosis in such patients, in addition to further studies to highlight the role of IL-18 binding protein [BP] and Th-2 cytokines [as IL-10] as possible antagonists to the antiviral action of IL-18. Finally future- large scales studies correlating IL-18 gene expression with markers of HCC progression are recommended to gain insight into the antitumor action of IL-18 as it would be a promising new strategy to control HCC