Serum Concentrations Of Macrophage Colony-stimulating Factor Research Articles

Serum macrophage colony-stimulating factor (M-CSF) in patients with Hodgkin lymphoma

Macrophage colony-stimulating factor (M-CSF) was recently implicated by in vitro studies as a survival and proliferation factor for Hodgkin/Reed-Sternberg cells. We evaluated pre-treatment serum M-CSF levels in 66 patients with histopathologic diagnosis of classical Hodgkin lymphoma (HL) and looked for possible correlations with baseline clinical characteristics. Significantly higher M-CSF serum concentrations were found in patients with bulky mediastinal mass, systemic symptoms, and elevated ESR but not LDH. There was no significant association between M-CSF level and sex, clinical stage, number of lymph node areas involved, and histopathological subtype of HL. We conclude that serum M-CSF levels are frequently elevated in HL patients and are significantly related to the presence of bulky mediastinal mass and systemic symptoms. These observations may indicate a pathogenetic role of M-CSF in Hodgkin lymphoma.

The Role of Macrophage Colony-Stimulating Factor in Patients With Acute Myocardial Infarction

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.

Clinical significance of serum macrophage-colony stimulating factor (M-CSF) in esophageal cancer patients and its comparison with classical tumor markers

Hematopoietic growth factors (HGFs), such as macrophage-colony stimulating factor (M-CSF) are produced aberrantly in many malignancies. Esophageal cancer (EC) is characterized by late diagnosis, rapid progression and poor survival. The purpose of the present study was to determine the clinical usefulness of M-CSF in the diagnosis of EC and its histological type - squamous cell cancer of the esophagus (ESCC). The study included 80 patients with EC (54 with ESCC and 26 with adenocarcinoma of the esophagus) and 30 healthy subjects. The serum concentrations of M-CSF, carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) were determined using immunoenzyme assays. We defined the percentage of increased concentrations of proteins tested and the areas under the receiver-operating characteristics (ROC) curves. In EC and ESCC patients, serum concentrations of M-CSF, CEA and SCC-Ag were significantly higher compared with healthy subjects. Concentrations of M-CSF in both groups analyzed (EC and ESCC) showed a tendency for increases with depth of tumor invasion, the presence of lymph node and distant metastases. The combined use of M-CSF with SCC-Ag increased their percentage of increased concentrations, and this value was higher than for classical tumor markers in both groups analyzed. The area under ROC curve for M-CSF was larger than for CEA in EC patients. Our findings suggest the potential usefulness of serum M-CSF concentrations as a tumor marker for EC, especially in combination with SCC-Ag. However, the diagnostic value of this cytokine may be limited because of its non-specific nature.

Elevated levels of macrophage colony‐stimulating factor in human fracture healing

Macrophage colony-stimulating factor (M-CSF) plays a unique role in bone remodeling. However, to our knowledge, no data on the role of M-CSF in fracture healing in humans have been published so far. This study addressed this issue. One hundred and thirteen patients with long-bone fractures were included in the study and divided into two groups, according to their course of fracture healing. The first group contained 103 patients with normal fracture healing. Ten patients with impaired fracture healing formed the second group of the study. Volunteers donated blood samples as control. Serum samples were collected over a period of 6 months, following a standardized time schedule. In addition, M-CSF levels were measured in fracture hematoma and serum of 11 patients with bone fractures. M-CSF concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Fracture hematoma contained significantly higher M-CSF concentrations compared to M-CSF concentrations in patient's serum. M-CSF levels in fracture hematoma and in patient's serum were both significantly higher than M-CSF concentrations measured in serum of healthy controls. Highly elevated M-CSF serum concentrations were found in patients with physiological fracture healing over the entire observation period. Significant differences in the M-CSF serum concentration between patients with normal fracture healing and patients with impaired fracture healing were not observed. This study indicates, for the first time, to our knowledge, a possible local and systemic involvement of M-CSF in humans during fracture healing.

Increased macrophage colony-stimulating factor levels in patients with Graves’ disease

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves' disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.

Changes in urinary and serum concentrations of macrophage-colony stimulating factor (M-CSF) in patients with renal diseases

Background. The infiltration of monocytes/macrophages into renal tissues is a typical feature of progressive renal diseases. Macrophage-colony stimulating factor (M-CSF) is one of the cytokines that are required for the activation of macrophages. It was previously reported that the glomerular expression of M-CSF was increased in patients with mesangial proliferative glomerulonephritis and that the urinary and serum M-CSF concentrations were increased in IgA nephropathy. In this study, we measured the urinary and serum M-CSF concentrations in patients with renal diseases to elucidate the role of M-CSF and macrophages in the progression of renal diseases. Methods. We examined urinary and serum M-CSF concentrations in patients with IgA nephropathy (IgA-N), lupus nephritis (LN), minimal change nephrotic syndrome (MCNS), and membranous nephropathy (MN), and in normal controls. The M-CSF concentrations were compared with the clinical parameters and the histological changes. These concentrations were also compared with the number of glomerular macrophages in the IgA-N group. In addition, the effects of prednisolone therapy on the M-CSF concentrations were examined in the patients with IgA-N. Results. Urinary and serum M-CSF concentrations were increased in the severe IgA-N group, the severe LN group, and the MCNS group (nephrotic) compared with concentrations in the control group. Urinary and serum M-CSF concentrations were correlated with the degree of proteinuria, mesangial proliferation, and the number of glomerular macrophages in IgA-N and LN. In addition, the urinary and serum M-CSF concentrations were decreased with prednisolone therapy in the patients with IgA-N. Conclusions. Urinary and serum M-CSF concentrations were elevated in patients with severe stage of mesangial proliferative glomerulonephritis and were correlated with the amount of urinary protein excretion, mesangial proliferation, and glomerular macrophage infiltration. Urinary and serum M-CSF concentrations may be useful markers with which to assess the extent of glomerular changes in mesangial proliferative glomerulonephritis.

Serum Levels of Macrophage Colony-Stimulating Factor and Aortic Calcification in Hemodialysis Patients

Hemodialysis (HD) patients have accelerated atherosclerosis. Recent reports have shown that aortosclerosis is more frequently observed in HD patients than in healthy subjects. Macrophage colony-stimulating factor (M-CSF) secreted by activated macrophages may be involved in the process of aortosclerosis in HD patients. To understand the mechanism behind the increased incidence of aortosclerosis in HD patients, we examined the relationships between serum M-CSF levels and aortic calcification index (ACI) estimated by CT scan. A significant increase in serum M-CSF concentrations was found in HD patients (3.8 ± 0.2 ng/ml) as compared with controls (1.5 ± 0.1 ng/ml). No significant differences were observed between chronic glomerulonephritis and diabetes mellitus groups of patients. We also found no significant differences between the groups using different membranes (triacetate 3.8 ± 0.2 ng/ml vs. polysulfone 3.8 ± 0.4 ng/ml). There was no correlation between serum M-CSF concentrations and clinical parameters such as age, duration of HD, blood pressure, serum concentrations of nitrogen, creatinine, cholesterol, triglyceride, LDL, Ca × P products, and intact parathyroid hormone. A positive correlation was observed between serum M-CSF levels and ACI in HD patients (r = 0.596, p < 0.01). These results suggest that M-CSF may be involved in the process of aortosclerosis in HD patients.

Increased Urinary Excretion of Macrophage-Colony-Stimulating Factor (M-CSF) in Patients with IgA Nephropathy: Tonsil Stimulation Enhances Urinary M-CSF Excretion

Upper respiratory tract infection including chronic tonsillitis is considered to be involved in the onset and/or the progression of IgA nephropathy. It is well known that deterioration of urinary findings occurs after episodes of upper respiratory tract infection in patients with IgA nephropathy. We previously showed that the expression of macrophage-colony-stimulating factor (M-CSF) is increased in the glomeruli of patients with IgA nephropathy and correlated with glomerular mesangial proliferation, suggesting that M-CSF plays an important role in the progression of IgA nephropathy. In the present study, we measured the serum and urinary concentrations of M-CSF in patients with IgA nephropathy associated with chronic tonsillitis. Furthermore, we evaluated the effects of the local provocation test of tonsils (mechanical tonsil stimulation) on the serum and urinary concentrations of M-CSF in the following three groups: (1) IgA nephropathy with severe mesangial proliferation, (2) IgA nephropathy with mild mesangial proliferation, and (3) patients with chronic tonsillitis without renal disease. The serum and urinary levels of M-CSF in the groups with severe and mild IgA nephropathy were significantly higher than those in the chronic tonsillitis group. The urinary M-CSF level but not the serum M-CSF level was positively correlated with the degrees of mesangial proliferation and glomerular M-CSF expression in the renal biopsy specimens. The urinary M-CSF concentration was significantly increased after tonsillitis stimulation in both mild and severe IgA nephropathy groups. Enhanced urinary excretion of M-CSF prolonged for 7 days after tonsil stimulation in the severe IgA nephropathy group; in contrast, the urinay M-CSF level was increased for only 2 days after tonsil stimulation in the mild IgA nephropathy group. The urinary M-CSF level was not changed in the chronic tonsillitis group after tonsil stimulation. The serum concentrations of M-CSF were not changed after tonsil stimulation in these three groups. Our present results suggest that tonsil stimulation contributes to the progression of IgA nephropathy via enhancement of glomerular production of M-CSF. The urinary excretion of M-CSF may be a useful predictor to evaluate the relevance of chronic tonsillitis to the disease and the indication of tonsillectomy in patients with IgA nephropathy.

Bone disease in multiple myeloma.

Bone disease in multiple myeloma.

Changes in macrophage colonystimulating factor concentration in serum and follicular fluid in in-vitro fertilization and embryo transfer cycles

Objective: To evaluate the changes of macrophage colony-stimulating factor concentration in serum and compare macrophage colony-stimulating factor concentration in follicular fluid (FF) through IVF-ET cycles. Design: Sera and the matched FFs were collected serially through the IVF-ET cycles and analyzed retrospectively with respect to macrophage colony-stimulating factor concentration. Setting: Department of Obstetrics and Gynecology of Kumamoto University Hospital. Patient(s): Ninety-four women underwent 129 cycles of ovulation induction by using GnRH agonist (GnRHa)-hMG-hCG for IVF-ET program. Intervention(s): Serum and FF macrophage colony-stimulating factor concentrations were measured by ELISA. Main Outcome Measure(s): Concentrations of macrophage colony-stimulating factor in serum and FF. Result(s): Serum macrophage colony-stimulating factor concentration was gradually increased throughout ovarian stimulation, and reached a peak from the day of oocyte retrieval to 2 days after oocyte retrieval, whereas no significant change in macrophage colony-stimulating factor was observed in cases of poor ovarian response to hMG. The macrophage colony-stimulating factor concentration in follicles was significantly higher than that in sera on the day of oocyte retrieval, and the concentrations in follicles from which oocyte could be retrieved were significantly higher than those from which oocyte could not be retrieved. Conclusion(s): These results suggest that gonadotropins lead to an increase in ovarian macrophage colony-stimulating factor production, and that this macrophage colonystimulating factor production in response to hMG administration is lost in poor ovarian responders. Thus, macrophage colony-stimulating factor may play an important role in the process of follicular maturation and ovulation as an intraovarian regulator.

Thrombocytopenia in the Sepsis Syndrome: Role of Hemophagocytosis and Macrophage Colony-stimulating Factor

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients with the sepsis syndrome, but its mechanisms frequently remain undetermined. Hemophagocytosis has been reported as a cause of thrombocytopenia in various diseases. This prospective study was designed to assess: (1) the incidence of hemophagocytosis in patients suffering from both the sepsis syndrome and unexplained thrombocytopenia, and (2) the circulating level of the macrophage-colony-stimulating factor (M-CSF) according to the presence or absence of hemophagocytosis.METHODS: Fifty consecutive patients diagnosed with both the sepsis syndrome and thrombocytopenia of undetermined origin were studied. Hemophagocytosis was diagnosed based on microscopical examination of sternal bone marrow aspiration by two independent observers. Serum M-CSF concentrations were measured in each patient and compared with levels of a normal population (n = 59). Causes and severity of sepsis syndromes as well as serum M-CSF levels were compared beween patients with and without hemophagocytosis.RESULTS: Hemophagocytosis was diagnosed in 32 patients (64%). Mean serum M-CSF levels were increased in patients when compared with normal subjects (539 ± 141 versus 208 ± 82 IU/mL: P <0.001), and higher in patients with than without hemophagocytosis (580 ± 145 versus 457 ± 89 IU/mL: P = 0.01). Multiorgan dysfunction and infection were independent risk factors of hemophagocytosis (odds ratio = 31.3 and 6.8, 95% confidence interval (CI) = 5.4 to 177.6 and 1.0 to 47.4, P <0.0001 and P = 0.03, respectively).CONCLUSIONS: Hemophagocytosis is a frequent cause of unexplained thrombocytopenia in patients with severe sepsis syndrome. Our results suggest that M-CSF is overproduced in the sepsis syndrome, particularly when hemophagocytosis is present. The role of M-CSF in the initiation and development of hemophagocytosis remains to be determined.

The effects of prednisolone and interferons on serum macrophage colony stimulating factor concentrations in chronic hepatitis B

Backgrounds/Aims: Serum concentrations of macrophage-colony stimulating factor (M-CSF) are increased in parallel with hepatic inflammation. The aim of this study was to assess the immunologic significance of elevated M-CSF in patients with chronic hepatitis B virus infection. Methods: The subjects included 20 asymptomatic HBV carriers and 45 patients with chronic hepatitis B, including 8 undergoing prednisolone treatment, 10 experiencing an acute exacerbation, and 12 undergoing daily administration of interferons. Results: Serum concentrations of M-CSF significantly decreased during prednisole administration, but significantly increased following prednisolone withdrawal, similar to the increase during acute exacerbation. Changes in the lipopolysaccharide-stimulated production of interleukin-1-beta and tumor necrosis factor-alpha by peripheral whole blood, or of interferon-gamma by peripheral blood mononuclear cells showed a similar pattern. Serum concentrations of M-CSF did not correlate with the titers of HBV-DNA or HBV-DNA polymerase activity. However, serum M-CSF peaked preceding seroconversion to HBe antibody in three HBe antigen positive patients. Exogenous interferon-alpha, -beta, or -gamma induced significant elevation in serum in M-CSF concentrations, irrespective of changes in the serum alanine aminotransferase levels. Conclusions: Increased serum M-CSF is closely associated with increased serum interfersons and/or proinflammatory cytokines produced by peripheral blood cells during hepatic inflammation in chronic hepatitis B. This may be a consequence of the altered cytokine cascade resulting from the host immune response against hepatitis B virus.

Macrophage colony stimulating factor involvement in uremic patients

The immunodeficiency of patients with chronic renal failure (CRF) is related to multiple and complex alterations of the cytokine network and of its target cells such as T or B lymphocytes, monocytes, fibroblasts or endothelial cells. Chronic activation of monocytic functions is recognized as a key factor in these immunological disorders. Since macrophage colony stimulating factor (M-CSF) is essential for the activation of several functions of monocytes and macrophages and their production of cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, we investigated its involvement in patients with CRF. When measured by ELISA, M-CSF serum levels were significantly higher in patients with progressive CRF and those on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) than in controls. M-CSF serum levels did not correlate with the degree of renal insufficiency and were probably related to complex alterations in its production and/or degradation by the specific M-CSF receptors of macrophages. In HD patients the M-CSF serum concentrations inversely correlated with the number of circulating lymphocytes and were significantly higher in anemic patients requiring treatment with erythropoietin. Our results suggest that M-CSF may play a role in altering the immune system in uremic patients by maintaining in the circulation and tissues permanently primed monocytes and/or macrophages that can then be triggered to an activated state by secondary stimuli such as endotoxins, complement components, other cytokines or contact with foreign surfaces.

Effect of Listeria monocytogenes infection on serum levels of colony-stimulating factor and number of progenitor cells in immune and nonimmune mice

Studies were performed to determine changes in serum macrophage colony-stimulating factor (M-CSF) levels and the number of macrophage progenitor cells in bone marrow and spleens of nonimmune and immune mice infected with Listeria monocytogenes. Immunity in mice was established by infecting mice 6 weeks before use with a sublethal dose of L. monocytogenes. When challenged with 10(4) L. monocytogenes organisms, immune mice had an early (12 h) peak in M-CSF serum concentrations. Levels remained elevated for 24 h but fell towards normal by 48 h. By contrast, M-CSF levels in nonimmune mice did not rise until 24 h after challenge, remained elevated for 7 days, and returned to normal by 14 days. The number of macrophage progenitor cells in the bone marrow of immune mice rose slightly during infection, whereas the number in nonimmune mice fell significantly by days 4 and 7. Progenitor cells in spleens of immune mice more than doubled during infection; in nonimmune mice, a sixfold increase was noted. These results indicate that important parameters of monocyte production differ in immune and nonimmune mice during listeria infection and suggest a possible mechanism for differences in resistance to infection.