Percentage Of Peripheral Blood Monocytes Research Articles

Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study.

Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74-41.22; p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB.

Platelet depletion in mice increases mortality after thermal injury

AbstractPlatelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P < .001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P < .01) and neutrophils (P < .05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNFα (P < .001), IL-6 (P < .001), and MCP-1 (P < .05) were also elevated by 24 hours whereas levels of TGFβ1 were reduced between 24 and 36 hours following injury in platelet-depleted mice (P < .001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFβ1 modulate the systemic inflammatory response occurring after injury.

Macrophages contribute to the initiation of ischaemic acute renal failure in rats

Although neutrophils and T cells are important in mediating renal injury following ischaemia/reperfusion, the role of macrophages is still unknown. Using liposomal clodronate (LC), we investigated the effect of systemic monocyte-macrophage depletion on renal damage in ischaemic acute renal failure in rats. Male Sprague-Dawley rats were injected by LC or liposomal vehicle and underwent bilateral renal pedicle clamping (40 min) or sham ischaemia. Biochemical and histological renal damage was assessed and gene expression kinetics of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and monocyte chemoattractant protein-1 (MCP-1) using quantitative real-time reverse transcription-polymerase chain reaction were conducted at 4, 24 and 72 h after reperfusion. The percentage of peripheral blood monocytes and ectodysplasin-1-positive cells in liver decreased significantly in LC-treated animals at 24 h. Systemic monocyte-macrophage depletion resulted in (a) less severe tubular necrosis, (b) reduced inflammation and (c) reduced apoptosis of renal tubular epithelial cells. Gene expression kinetics showed that IL-6 gene expression peaked early at 4 h after reperfusion, followed by TNF-alpha, IL-1beta and MCP-1 expressions, which peaked at 24 h. Systemic monocyte-macrophage depletion significantly reduced these cytokine and chemokine gene expressions. These results suggest that macrophages are an important mediator in the initiation period of ischaemia/reperfusion injury and strategies that limit initial macrophage infiltration or activation can be useful in the treatment of acute renal failure.

Detection of altered T helper 1 and T helper 2 cytokine production by peripheral blood mononuclear cells in patients with multiple sclerosis utilizing intracellular cytokine detection by flow cytometry and surface marker analysis.

Production of T helper 1 and T helper 2 cytokines was investigated in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients by a newly described technique, detection of intracellular cytokines by flow cytometry in conjunction with immunophenotype analysis. T-cell gamma interferon (IFN-gamma) production and interleukin 10 (IL-10) production were examined after PBMC activation with T-cell mitogens at 5 and 24 h, and monocyte spontaneous production of IL-10 and production after PBMC activation with lipopolysaccharide (LPS) for 24 h were also examined. The data indicate that MS patients have decreased percentages of T cells capable of secreting IFN-gama compared with healthy controls, and this change is detectable at 5 and 24 h. the patients displaying decreased T-cell production of IFN-gamma were essentially confined to a group being treated with the newly approved drug Betaseron (berlex Labs, Cedar Knolls, N.J.), a recombinant form of IFN-beta (rIFN-beta 1b). By gating of the entire lymphocyte population, analysis of IFN-gama production in T cells (CD3+ versus that in non-T cells (CD3+) was possible. The percentage of IFN-gamma-producing lymphocytes that was made up of T cells was essentially unchanged between the Betaseron-treated patients, non-Betaseron-treated patients, and controls, indicating that the suppression of IFN-gamma production displayed by betaseron-treated MS patients was a nonspecific suppression of all IFN-gamma-producing lymphocytes as opposed to a suppression of T-cell production only. The data seem to indicate that treatment of MS with Betaseron corresponds to an inhibition of the lymphocyte's ability to produce IFN-gamma. No changes were detected in T-cell production of IL-10 at either time point. We also observed that MS patients in general appear to have small percentages of peripheral blood monocytes spontaneously producing slight but detectable levels of IL-10. No difference was seen regarding monocyte production of IL-10 after PBMC activation with LPS between MS patients and controls. Both populations responded with high percentages of monocytes producing IL-10. The data seem to indicate that treatment of MS with Betaseron, known to decrease the exacerbation rate of relapsing-remitting MS, corresponds to a suppression of peripheral blood lymphocyte production of IFN-gamma. Monocyte production of IL-10 may also play a role in regulating the disease process.

Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-alpha and interleukin-1 alpha concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-alpha and interleukin-1 alpha are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury.

Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-α, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-α and interleukin-1α concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-α and interleukin-1α are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury. (HEPATOLOGY 1991;13:267—276).

Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines.

The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.

Identification of cells of the human mononuclear phagocyte system with rat monoclonal antibodies.

Five rat monoclonal antibodies (McAbs) to human macrophages are described: YTH 8.18, YTH 25.7, YTH 51.1, YTH 85.12.1, and YHB 65.5. These McAbs are divided into three groups, since YTH 8.18, YTH 51.1, and YHB 65.5 are thought to identify the same antigen. These McAbs react with some bone marrow blast cells, granulocytes, and different percentages of peripheral blood monocytes. When studied on different body tissues, they were found to identify all members of the mononuclear phagocyte system (MPS), except Langerhans cells of skin and epithelium and in the case of one group (YTH 8.18/YTH 51.1/YHB 65.5) osteoclasts. In nine reactive lymph nodes the anti macrophage McAbs identified germinal centre macrophages, sinus macrophages, and interdigitating cells, but not dendritic reticulum cells. They also identified epithelioid macrophages and Langhans-type multi-nucleated giant cells in lymph nodes involved in granulomatous lesions (sarcoidosis and toxoplasmosis). In 24 cases of non-Hodgkin's lymphoma, the antimacrophage McAbs identified reactive macrophages in cases of B- or T-lymphocyte origin, whereas in three selected cases of true histiocytic lymphoma all the McAbs were found to be reactive with the vast majority of neoplastic macrophages as they were with the cells of a neoplastic macrophage line (U937). The possible use of these McAbs in the identification of benign and malignant macrophages in different systems is discussed.

Monocyte chemotaxis in leukemia patients.

Monocyte chemotaxis was studied in 35 patients with ALL, six with CLL, six with AML, and 10 with CML before beginning chemotherapy. Function was contrasted to age-matched control groups. Significant inhibition of chemotaxis was seen in patients with ALL (p less than 0.001) and CLL (p less than 0.01), whereas function in CML and AML patients was not significantly depressed. The deficient monocyte chemotaxis was not due merely to decreased percentages of peripheral blood monocytes. Thus, in addition to numerical deficiencies in monocyte numbers, qualitative deficiencies in monocyte function exist in patients with ALL and CLL.