Serum Macrophage Colony-stimulating Factor Levels Research Articles

Correlation of Serum M-CSF, CER, and TIMP-1 Levels with Liver Fibrosis in Viral Hepatitis.

Objective This research is aimed at investigating the relationship between liver fibrosis in viral hepatitis and macrophage colony-stimulating factor (M-CSF), tissue inhibitor of matrix metalloproteinase (TIMP-1), and ceruloplasmin (CER) in serum level. Methods Patients were randomly selected among those admitted to our hospital, and 60 healthy volunteers were chosen to serve as control participants. The levels of serum M-CSF, CER, and TIMP-1 were compared. According to the severity of their liver fibrosis, patients with CHB were separated into four groups: S1, S2, S3, and S4. Serum levels of M-CSF, CER, and TIMP-1 were correlated with liver fibrosis and hepatitis markers, and the diagnostic usefulness of the three indices was assessed with liver cirrhosis patients. Results Increases in M-CSF and TIMP-1 in the CHB group but decreases in CER were statistically significant (P < 0.05). Serum levels of M-CSF, CER, TIMP-1, HA, PC-III, C-IV, and LN differed significantly across the four study groups (P < 0.05). Over time, as liver fibrosis worsened, we observed a progressive uptick in M-CSF, TIMP-1, LN, HA, C-IV, and PC-III levels and a progressive downtick in CER levels, with significant (P < 0.05) differences between the groups. There was a significant positive correlation between liver fibrosis and serum M-CSF, PC-III, TIMP-1, HA, LN, and C-IV levels in the CHB group (P < 0.05) and a significant negative correlation between serum CER and these same factors (P < 0.05). The AUC of 0.956 for diagnosing the S4 stage was greater than that of 0.857, 0.851, and 0.817 for M-CSF, CER, and TIMP-1, respectively. Conclusions In CHB patients, the liver fibrosis degree is associated with the M-CSF, CER, and TIMP-1 levels, and the combined clinical detection of these three markers has better diagnostic significance.

Serum macrophage colony-stimulating factor levels in patients with essential hypertension after vaccination against SARS-CoV-2

The formation of immunity in the population to various variants of the COVID-19 pathogen is one of the most important problems for the world community. The aim of the study was to compare the dynamics of M-CSF and VEGF-A, IL-34 in the blood serum of patients with essential hypertension (EH) stage II, depending on the type of immunity formed (post-infectious, post-vaccination, “hybrid”) to analyze changes of M-CSF-mediated mechanisms of hypertension development. During the work, 2 groups of patients were formed: group 1-patients with stage II EH and SARS CoV-2 infection without pneumonia in the anamnesis, vaccination 6 months after laboratory recovery, group 2 – patients with stage II EH without COVID-19 in the anamnesis, vaccination during the follow-up period. Determination of M-CSF, IL-34, VEGF-A, IgG level to SARS-CoV-2 was determined using an enzyme-linked immunosorbent assay. The formation of post-infectious immunity in patients with stage II EH, despite the mild course of COVID-19, is accompanied by a long-term (up to 6 months) pathophysiologically significant increase in the serum level of M-CSF (p 0.001) with a decrease in IL-34 (p 0.001). Analysis of the dynamics of changes in M-CSF, IL-34, VEGF-A in the postvaccination period in the blood serum of patients with stage II EH with COVID-19 in the anamnesis (“hybrid” immunity), determined the absence (p 0.05) of changes in the levels of M-CSF, VEGF-A after the first component of “SPUTNIK V” against the background of an increase of the level of IgG to SARS-CoV-2. 21 days after the second component of the vaccine, an increase of M-CSF was detected when compared with both pre-vaccination indicators and data 21 days after the introduction of the first component of the vaccine (p 0.001). Comparing the dynamics of the of M-CSF, IL-34 and VEGF-A in patients with stage II EH without COVID-19 in the post-vaccination period with the data on the formation of “hybrid” immunity, an increase in M-CSF was recorded 21 days after the introduction of the first and second components against the background of a decrease in IL-34, but with the restoration of pre-vaccination concentrations in 100% of patients by day 180 with comparable immunogenicity after 180 days. In patients with EH II, the pathogenetic “summation” of the pre-infectious imbalance of cytokine regulation and postcovid changes is important, which in a number of patients may be the reason for the prolongation of the stabilization of the balance of the M-CSF-IL-34-VEGF-A system in the post-vaccination period during the formation of “hybrid” immunity.

Serum macrophage colony-stimulating factor levels in patients with essential hypertension after SARS-CoV-2 infection

Understanding changes in the cytokine-mediated mechanisms in immunopathogenesis of essential hypertension (EH) after COVID-19 poses a pressing scientific issue. SARS-CoV-2 exerts direct effects on macrophages with high probability altering regulatory M-CSF-VEGF-A-IL-34 axis, thereby accounting for change in cytokine-mediated patterns of hypertension progression. Immunopathogenesis of complications after SARS-CoV-2 infection and a role of M-CSF in EH pathogenesis justify study objective – to compare the serum M-CSF and VEGF-A, IL-34 levels in stage II EH patients prior to COVID-19 and one month after recovery to assess modality of altered M-CSF-mediated mechanisms behind hypertension progression. Four groups of patients were stratified depending on EH and clinical characteristics of COVID-19 (without/with pneumonia). Blood sampling was performed one month after COVID-19. The serum M-CSF and VEGF-A, IL-34 level was measured by using enzyme-linked immunosorbent assay. The data were statistically processed by using Stat Soft Statistica 13.5. Comparative analysis of serum M-CSF level in patients with stage II EH prior and after COVID-19 revealed that regardless of clinical course (with/without pneumonia) they were featured with higher levels of M-CSF one month after recovery (p 0.001) vs baseline level. The serum VEGF-A level in patients with stage II EH did not change in papallel with increased M-CSF (458 pg/ml or more) one month after SARS CoV 2 infection. However, M-CSF stimulated rise in serum VEGF-A level and accounted for formation of marked coronary collateral network prior to infection. A relationship between the increased serum M-CSF level (higher than 392 pg/ml) and elevated percentage of COVID-19 with pneumonia in patients with stage II EH prior to the infection might be related to the hypothesis about “a role of dysregulated activation of mononuclear phagocytes in development of lung tissue damage”. The data presented prove scientific and clinical value of assessing a role for M-CSF with respect to altered cytokine-mediated patterns of EH progression after COVID-19 recovery.

New Insight into Atherosclerosis in Hemodialysis Patients: Overexpression of Scavenger Receptor and Macrophage Colony-Stimulating Factor Genes

Background: Scavenger receptors (SRs) play a pivotal role in atherogenesis. The mechanism of atherosclerosis, which is specific to hemodialysis (HD) patients, was studied on the basis of SR gene expressions. Methods: The gene expressions of SR type A (SR-A) and CD36 were studied in peripheral monocytes by real-time reverse transcription polymerase chain reaction. Data were compared between HD (n = 30) and age-matched control subjects (n = 10). Serum levels of macrophage colony-stimulating factor (M-CSF) were measured with enzyme-linked immunosorbent assay to test its role in SR expression. The statistical differences and associations between two continuous variables were assessed using the Mann-Whitney U test and Pearson's correlation coefficient, respectively. Results: The relative quantities of SR mRNAs were significantly greater in HD patients than in controls [median (interquartile range): SR-A, 1.67 (0.96-2.76) vs. 0.90 (0.60-1.04), p = 0.0060; CD36, 1.09 (0.88-1.74) vs. 0.74 (0.64-0.99), p = 0.0255]. The serum concentration of M-CSF was significantly higher in HD patients than in controls [1,121 (999-1,342) vs. 176 (155-202) pg/ml, p < 0.0001]. In addition, the relative quantity of M-CSF mRNA was significantly greater in HD patients than in controls [0.79 (0.42-1.53) vs. 0.42 (0.28-0.66), p = 0.0392]. The serum M-CSF levels were positively correlated with both the relative quantity of SR-A mRNA (r² = 0.1681, p = 0.0086) and that of CD36 mRNA (r² = 0.1202, p = 0.0284) in all subjects (n = 40). Conclusion: HD patients are predisposed to atherosclerosis as a consequence of their enhanced monocyte SR expressions. SRs and M-CSF are potential therapeutic targets for atherosclerosis in this high-risk population.

Macrophage colony-stimulating factor (M-CSF) in first trimester maternal serum: correlation with pathologic pregnancy outcome.

To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies. This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free β-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling. 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270±91 pg/ml (p=0.032), whereas cases of trisomy 13 (183±68 pg/ml) and trisomy 18 (143±40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free β-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M-CSF. M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research.

Macrophage colony‐stimulating factor plays a pivotal role in chemically induced hepatocellular carcinoma in mice

The specific purpose of this study was to investigate the role of macrophage colony-stimulating factor (M-CSF) in initiation and progression of hepatocellular carcinoma using M-CSF-deficient mice. M-CSF-deficient (osteopetrotic: op/op) and their littermate (LM) mice were i.p. injected with diethylnitrosamine (DEN) to induce hepatocellular carcinoma. Twenty-eight weeks after DEN administration, the tumor incidence rate and serum M-CSF levels were assessed. Furthermore, distribution of the activated macrophages and the mRNA expression of CD163 and CD204 were evaluated. Moreover, angiogenesis was analyzed in tumors. In another set of experiments, apoptosis and proliferation of the hepatocytes were examined in the acute phase after DEN administration. Isolated hepatic macrophages were cultured with or without M-CSF, and vascular endothelial growth factor (VEGF) production was assessed by enzyme-linked immunoassay. Tumor incidence was significantly reduced in the op/op compared with the LM mice. Serum M-CSF levels were increased in the carcinogenesis models of the LM mice. Hepatic macrophages were found only in tumors in the op/op but in both normal liver tissue and tumors in the LM mice. In the op/op group, the mRNA expression of inflammatory cytokines was significantly lower compared with the LM mice. Furthermore, apoptosis was significantly increased in the op/op than the LM mice. Angiogenesis increased in liver tumors from the LM compared with the op/op mice. Production of VEGF was greater in the hepatic macrophages incubated with M-CSF compared with those without M-CSF. Thus, M-CSF is involved in the progression of chemically induced hepatocarcinogenesis.

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.

Effects of raloxifene on serum macrophage colony-stimulating factor and interleukin-18 levels in postmenopausal women younger than 60 years

Macrophage colony-stimulating factor (M-CSF) and interleukin-18 (IL-18) are cytokines expressed predominantly in atheromatous plaque, and overproduction of these has been found to be associated with coronary artery disease. The aim of this study was to investigate the effect of raloxifene, a selective estrogen receptor modulator, on serum M-CSF and IL-18 levels, cytokines that are presumably involved in the pathogenesis of atherosclerosis. A total of 70 postmenopausal women (age, 56.45 ± 1.52 y) without previously confirmed cardiovascular disease were enrolled in a 6-month prospective, randomized, controlled study. Women were randomly assigned to two groups: 35 women received oral administration of 60 mg/day raloxifene for 6 months and 35 were in the control group and received no medications. Serum lipid concentrations and high-sensitivity C-reactive protein (hs-CRP), M-CSF, and IL-18 levels were measured at baseline and at the sixth month in both groups. Compared with the control group, the raloxifene group had a significant decrease in serum IL-18 concentrations and a 25.29% reduction in serum hs-CRP concentrations. M-CSF levels were reduced by 5.94% in the raloxifene group, but the difference was not statistically significant. At the sixth month, 60 mg/day of raloxifene significantly decreased the median serum total cholesterol and low-density lipoprotein cholesterol levels when compared with the baseline levels. Raloxifene reduces serum total cholesterol, low-density lipoprotein cholesterol, hs-CRP, and IL-18 levels. According to the results of our study, it is suggested that raloxifene may have a favorable effect on the prevention of cardiovascular disease in healthy postmenopausal women younger than 60 years.

Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases

To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis. The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-alpha, interleukin 6, interferon-gamma, ferritin, and beta2-microglobulin (beta2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered. Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still's disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and beta2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; beta2m: 18.8 vs 5.4 mg/dl, p = 0.0058). The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ss(2)m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.

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.

Increase in the level of macrophage colony-stimulating factor in patients with systemic lupus erythematosus

Macrophage colony-stimulating factor (M-CSF) primarily regulates the survival, proliferation and function of macrophages.1 Studies on MRL- Faslpr mice demonstrate that M-CSF plays a pivotal role in kidney injury.2–4 Increased glomerular...

Serum level of macrophage colony-stimulating factor is increased in prostate cancer patients with bone metastasis

Recent evaluation of human prostate tissues has shown predominantly high expression of the macrophage colony-stimulating factor receptor in prostatic intra-epithelial neoplasia or prostate cancer. However, the expression of its ligand, the macrophage colony-stimulating factor (M-CSF), and the biological role of this signaling in prostate cancer has not been analyzed. In this research we determined the relationship of serum M-CSF level to clinical parameters of prostate cancer progression. We measured the serum level of M-CSF in 170 patients with histologically confirmed prostatic adenocarcinoma and in 54 patients in whom prostate cancer was not detected. We also investigated the M-CSF expression in prostate cancer tissues by immunohistochemistry. The serum levels of M-CSF in bone metastatic prostate cancer patients was significantly higher than those in non-metastatic patients, while M-CSF did not differ with regards to histological grade, Gleason score or local tumor progression. M-CSF expression was detected in prostate cancer cells themselves by immunohistochemistry. These results suggest that M-CSF may have a functional role in prostate cancer progression.

Elevated serum M-CSF level predicts reduced survival in metastatic breast cancer patients

10591 Background: Macrophage colony stimulating factor (M-CSF) and its receptor (CSF-1R, the c-fms oncogene protein product) have been reported to be expressed in a variety of cancers, including breast cancer. The M-CSF produced by breast cancer cells and surrounding stromal cells increases osteoclast formation and maturation and enhances the expression of stromal RANK ligand, both of which increase osteolytic bone degradation. In this study we evaluated the predictive and prognostic potential of circulating M-CSF in metastatic breast cancer patients treated with hormone therapy. Methods: Using an M-CSF ELISA (R&amp;D Systems, Minneapolis, MN), M-CSF concentration was determined in pretreatment sera from 204 metastatic breast cancer patients enrolled in a phase III 2nd-line hormone therapy trial of fadrozole vs. megace, and also in sera from 25 post-menopausal control female subjects. Results: The serum M-CSF level from the 25 healthy post-menopausal female control subjects had a mean ± SD of 835.6 ± 276.1 pg/ml (range 319.0 - 1,465.8 pg/ml). The upper limit of normal was defined as the 95th percentile of the serum M-CSF level from the female control group (1277 pg/ml). Pretreatment serum M-CSF levels from the metastatic breast cancer patients ranged from 82.2 - 3,019.8 pg/ml, and were found elevated above the upper limit of normal in 15 of 204 patients (7.35 %). Patients with elevated pretreatment serum M- CSF did not have a significantly different objective response rate, clinical benefit rate, or time to progression to hormone therapy; but these patients did have significantly reduced overall survival (median survival 10.0 months) compared to patients with normal serum M-CSF levels (median survival 24.3 months)(p = 0.007). In multivariate analysis with serum HER-2/neu included as a covariate, elevated serum M-CSF level remained a significant independent variable for reduced survival (p= 0.032). Conclusions: Pretreatment serum M-CSF levels were elevated in 7 % of metastatic breast cancer patients compared to healthy female control subjects, and these patients had significantly reduced overall survival. Serum M-CSF deserves further study to determine its predictive and prognostic biomarker potential in breast cancer patients. No significant financial relationships to disclose.

Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis

Background Elevated serum concentrations of macrophage-colony stimulating factor (M-CSF) have been found in a variety of malignant diseases. The aim of our study was to assess correlations between serum levels of M-CSF and clinicopathological features and survival rates in patients with colorectal cancer (CRC). Patients/methods M-CSF and the established tumor markers (carcinoembryonic antigen — CEA and carbohydrate antigen — CA 19-9) were investigated in the sera of 116 colorectal cancer patients and correlated with the clinical parameters of the disease and with the survival of patients. We compared M-CSF serum levels in CRC with colorectal adenoma patients. M-CSF was determined using enzyme-linked immunosorbent assay (ELISA). Tumor markers were measured by microparticle enzyme immunoassays (MEIA). Results CRC patients had significantly higher M-CSF and tumor markers levels compared to healthy controls and colorectal adenoma patients, with a significant association between M-CSF levels, disease stage and lymph node metastasis. Serum levels of M-CSF and CEA decreased significantly after radical resection of the tumor. Moreover, the multivariate analysis showed that the serum level of M-CSF in CRC patients was an independent prognostic factor. Conclusion These findings suggest the potential clinical use of circulating M-CSF measurements, particularly in estimating prognosis for patients with CRC.

Serum Levels of Macrophage Colony-stimulating Factor in Singleton and Twin Pregnancy

Macrophage colony-stimulating factor (M-CSF) is present in the placenta and has been implicated in placental growth and development. M-CSF levels in peripheral blood increase significantly with progression of pregnancy in uncomplicated singleton pregnancy. This study investigated whether serum M-CSF levels in singleton pregnancy differed from those in twin pregnancy. A hundred and four pregnant women, of whom fifty-nine were women carrying single fetuses and forty-five were women with twin fetuses, participated in the study. Their average gestational age at entry was 10, 20, 30, and 38 weeks of gestation in singleton pregnancy and 10, 20, 30, and 35 weeks in twin pregnancy. Peripheral blood was collected and serum was separated after centrifugation and stored at - 20 degrees C. M-CSF levels were determined by ELISA. In both groups, the serum levels of M-CSF increased significantly as pregnancy progressed. M-CSF levels were relatively higher in twin pregnancy than in singleton pregnancy at 10, 20, and 30 weeks. At 35 and 38 weeks, the M-CSF levels were significantly higher in twin pregnancy than in singleton pregnancy. Elevation of serum M-CSF supports M-CSF production in the placenta. This elevation in twin pregnancy may be related to increased demand of M-CSF in twin pregnancy.

Different Effects of Simvastatin and Losartan on Cytokine Levels in Coronary Artery Disease

Use of HMG-CoA reductase inhibitors (statins) and angiotensin II type 1 (AT(1)) receptor antagonists reduces the incidence of cardiovascular events. The cytokines macrophage colony-stimulating factor (M-CSF) and transforming growth factor (TGF)-beta may exert proatherogenic and antiatherogenic effects, respectively. In this study, we examined whether treatment with a statin or an AT(1) receptor antagonist alters M-CSF and TGF-beta levels in patients with coronary artery disease. Twenty-seven consecutive patients with coronary artery disease were randomly assigned to the following three treatment groups for 8 weeks: simvastatin 5 mg/day (n = 10); losartan 50 mg/day (n = 9); or control (usual treatment; n = 8). Blood samples were collected before and after treatment. Clinical characteristics and baseline cytokine levels were comparable among the three groups. Serum levels of M-CSF were significantly decreased only in the simvastatin group (from 403 +/- 71 to 303 +/- 116 pg/mL; p = 0.009). Plasma levels of TGF-beta were significantly increased only in the losartan group (from 5.01 +/- 1.13 to 7.50 +/- 3.83 ng/mL; p = 0.021). Simvastatin decreased serum M-CSF levels independently of changes in total cholesterol or low-density lipoprotein-cholesterol. The results of this study indicate that simvastatin decreases serum levels of M-CSF while losartan increases plasma levels of TGF-beta, suggesting that the two drugs may have different anti-atherosclerotic properties.

Significance of increased level of serum macrophage colony-stimulating factor in patients with preeclampsia

To explore the role of macrophage colony-stimulating factor (MCSF) in the pathogenesis of preeclampsia. By ELISA method, MCSF concentrations were determined in serum samples obtained from 39 patients with preeclampsia and 40 normal pregnant women as controls. The concentrations of serum MCSF were compared between preeclampsia and normal pregnancy, and between early-onset and late-onset preeclampsia. Serum MCSF concentrations were significantly higher in preeclamptic women than those in controls (431.0 kIU compared with 179.1 kIU, P<0.001). There were no significant differences in serum MCSF levels between early-onset and late-onset preeclampsia (P>0.05). Serum MCSF was not correlated with maternal age, gestational age, and placenta weight (P>0.05 for all). Increased level of serum MCSF is an important indicator of preeclampsia and it may play a role in the pathogenesis of the disease.

Predictive value of serum macrophage colony-stimulating factor for development of aortic calcification in haemodialysis patients: a 6 year longitudinal study

Accelerated atherosclerosis is a major complication in patients on haemodialysis (HD). Macrophage colony-stimulating factor (MCSF) is a representative regulator of activation of monocytes and macrophages, and plays important roles in the development of atherosclerosis in HD patients. However, the long-term predictive value of the serum MCSF level for the development of aortic calcification under HD conditions has not been reported. Serum MCSF level was measured in 40 HD patients. The aortic calcification index (ACI) was also calculated on computed tomography once each year for 6 years. Predictive value was examined by logistic regression analysis. At baseline, there was a significant correlation between serum MCSF and ACI (r = 0.43, P<0.01). A significant increase in ACI was first noted at 4 years post-baseline and the increase was maintained thereafter in the high MCSF group. No such changes were noted in the low MCSF group. Univariate analysis identified high levels of calcium x phosphorus product, triglyceride, C-reactive protein (CRP), MCSF and presence of diabetes mellitus as significant predictors for increased ACI at 6 years. However, among these five factors, high levels of CRP and MCSF were the only independent and significant predictors (odds ratio = 24.0, P = 0.03 and odds ratio = 22.8, P = 0.02, respectively). Our results demonstrated that MCSF is associated with the process of atherosclerosis in HD patients. Furthermore, the serum MCSF level is an independent long-term predictor of increased ACI. These results provide useful information for preventive strategies against atherosclerotic disease under HD conditions.

Hematopoietic cytokines in the sera of patients with pancreatic cancer

Hematopoietic cytokines (HCs) can affect the growth and spread of cancer. Therefore, in the present study, we investigated in pancreatic cancer patients the serum levels of selected HCs, such as stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) in relation to a control group and to a group of patients with chronic pancreatitis. Classical tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum level of cytokines with the tumor stage. The diagnostic sensitivity, specificity, positive and negative predictive values and receiver-operating characteristics (ROC) curve for cytokines and classical tumor markers were defined. The cytokines were measured in 48 patients with pancreatic cancer, in 23 patients with chronic pancreatitis and in 40 healthy subjects. HCs were determined using ELISA. CEA and CA 19-9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, IL-3, GM-CSF, M-CSF, CEA and CA 19-9 in the pancreatic cancer patients compared to the control group. The serum levels of M-CSF and tumor markers were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of SCF, M-CSF and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels in the pancreatitis group correlated positively with the tumor markers tested--CEA and CA 19-9. The diagnostic sensitivity of SCF and specificity of M-CSF and tumor markers were the highest. The SCF and M-CSF areas under the ROC curve were greater than the areas for other cytokines. These results suggest the potential usefulness of HCs in pancreatic cancer detection; however, further investigations of early-stage pancreatic cancer patients and confirmation by a prospective study are necessary.

Serum levels of macrophage-colony stimulating factor (M-CSF): a marker of kidney allograft rejection.

Macrophage-colony stimulating factor (M-CSF) is the principal factor for survival of monocytes and macrophages that play an important role in allograft rejection. We studied M-CSF serum levels during successful renal transplantation and acute graft rejection. A total of 114 kidney allograft recipients were assessed for M-CSF levels by enzyme-linked immunosorbent assay (ELISA). M-CSF serum levels were elevated in pre-transplant haemodialysis patients (611+/-355 IU/ml vs 168+/-61 in normal controls, P<0.01). Following successful renal transplantation, M-CSF decreased in the first month, stabilizing at 257+/-222 IU/ml (not significantly different from normal controls) in 52 post-transplant stable patients. There was no correlation between M-CSF level and creatinine clearance. M-CSF levels increased significantly (2-5 times) during biopsy-proven acute rejection episodes in 20 of 25 patients. All rejection episodes were successfully treated and serum M-CSF decreased rapidly to pre-rejection levels in 17/20 patients. In contrast, in five patients with cyclosporin toxicity and four patients with other causes of allograft dysfunction, M-CSF serum levels did not change. M-CSF serum level might be a specific marker of acute rejection. The source of increased production during rejection warrants further investigation, with infiltrating T cells and resident kidney cells being likely candidates.