Serum Macrophage Colony-stimulating Factor Research Articles

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.

Increased serum levels of macrophage colony-stimulating factor (M-CSF) in alpha- and beta-thalassaemia syndromes: correlation with anaemia and monocyte activation.

Serum levels of M-CSF were determined by an ELISA method in 29 and 34 patients with HbH disease (alpha 1/alpha 2 or alpha 2/HbCS) or beta zero-thal/HbE, respectively, in 28 haematologically normal subjects and in five patients with anaemia due to iron deficiency or myelodysplasia. In HbH disease and beta zero-thal/HbE, M-CSF concentrations were significantly higher than those in the normal subjects [986 +/- 138 and 1385 +/- 133, respectively, vs. 500 +/- 33 pg/ml (mean +/- SEM); p < 0.01, and p < 0.001, respectively]. By contrast, in patients with anaemia due to iron deficiency, M-CSF levels were within the normal range. In HbH disease and in beta zero-thal/HbE, M-CSF levels correlated inversely with mean basal Hb values (r = -0.39, p = 0.05 and r = -0.60, p < 0.001, respectively). In addition, in some of the HbH and beta zero-thal/HbE patients, monocyte ADCC activities towards red cells were tested and found to be approximately twice as high as those in normal controls [38.3 +/- 5.7 and 30.7 +/- 4.6 vs. 17.8 +/- 1.8% specific lysis (mean +/- SEM), respectively; p < 0.01 and p < 0.02, respectively]. When thalassaemic patients and normal controls were considered together there was a significant correlation between M-CSF levels and monocyte ADCC activities (r = 0.51, p < 0.02). The results suggest that in HbH disease and in beta zero-thal/HbE, raised serum M-CSF contributes to the anaemia by enhancing the effector function of mononuclear phagocytes towards red cells.

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.

Monocytosis and high serum macrophage colony-stimulating factor in Waldenstrom's macroglobulinemia [letter

Monocytosis and high serum macrophage colony-stimulating factor in Waldenstrom's macroglobulinemia [letter

Macrophage colony-stimulating factor in patients with rheumatoid arthritis

Macrophage colony-stimulating factor (M-CSF) is a cytokine involved in the development and proliferation of the monocyte/macrophage lineage cells. M-CSF has also been reported to participate in the induction of osteoclasts, and may be important in the destruction of bone and cartilage and the periarticular osteoporotic changes seen in patients with rheumatoid arthritis (RA). We developed a new ELISA technique to measure M-CSF levels in synovial fluid with high sensitivity and reproducibility. The mean M-CSF level in the synovial fluid of patients with RA was 1.38 +/- 0.56 ng/ml, and that of patients with osteoarthritis (OA) was 0.67 +/- 0.13 ng/ml. In contrast, serum levels of M-CSF in patients with RA and in normal controls were 1.32 +/- 0.50 ng/ml and 0.90 +/- 0.09 ng/ml, respectively. These differences were both statistically significant. Since serum M-CSF levels correlate with inflammatory signs obtained from examination of blood, they indicate the general condition of patients with RA. Synovial fluid M-CSF levels increase even in the early phase of RA and remain high despite drug therapy, which suggests that they reflect the condition of affected joints including joint spaces and inflamed synovia more directly than do the levels of serum M-CSF. Measurement of the M-CSF level in the synovial fluid may be useful in the diagnosis, clinical evaluation, and assessment of the effects of treatment in patients with RA.

Serum level of macrophage colony-stimulating factor as a marker for gynecologic malignancies.

We determined the serum levels of macrophage colony-stimulating factor (M-CSF) in 441 women with gynecologic diseases to evaluate its role as a marker for gynecologic malignancy. Serum M-CSF levels were above the normal baseline level of 1,056 U/ml in 64% (56/88) of patients with ovarian cancer, 27% (16/60) of those with cervical cancer, and 25% (15/61) of those with endometrial cancer. M-CSF was significantly elevated in the serum of patients with advanced as compared with early stage cancer (stage I) of the ovary (p < 0.01), cervix (p < 0.05), and endometrium (p < 0.05). Only 5.6% of the patients with benign ovarian tumors and 7.0% of those with endometrial cysts had serum levels of M-CSF that exceeded 1,056 U/ml. M-CSF was localized in the glandular epithelial cells as well as in the stromal macrophages and the endothelial cells of the ovarian cancers. M-CSF thus appeared to be a marker with high specificity for ovarian cancer.

Elevated serum levels of macrophage colony stimulating factor during interferon-α therapy for chronic hepatitis C

We estimated the serum levels of macrophage colony stimulating factor (M-CSF) in patients with chronic hepatitis C who were treated with interferon-α (IFNα). In 12 patients who received 3 or 6 MU of natural IFNα, or 9 MU of recombinant IFNα daily for 2 weeks then three times a week, blood was collected every 24 h after injection of IFNα in the initial 7 days of the therapy. In all the patients, serum levels of M-CSF were significantly ( P < 0.05) higher 24 h after the first injection of INFα. After reaching plateau levels on the third day, M-CSF remained at high levels. In four patients who received 3 or 6 MU of natural IFNα daily for at least 2 weeks, blood was collected daily three times after the last injection of IFNα. In all four patients, serum M-CSF levels gradually fell to the pre-treatment levels after 72 h. In six patients who received 3 or 6 MU of natural IFNα for 8 weeks, blood was collected before, during, and after the therapy. In these patients, serum M-CSF levels continued to be high during the therapy and decreased to pre-treatment levels after finishing the therapy. These results indicate that IFNα administration would increase serum levels of M-CSF in vivo.

Serum macrophage colony-stimulating factor (M-CSF) levels correlate with clinical response to interferon-alpha in patients with early-stage B-CLL.

Interferon-alpha (IFN-alpha) reduces peripheral lymphocyte counts in B-CLL (CLL). In eight patients with stage 0 CLL on IFN-alpha therapy, peripheral lymphocyte counts fell to 61.7 +/- 19.5% of baseline at week 2 (P < 0.01), while serum M-CSF levels rose from 455 +/- 183 U/ml to 686 +/- 110 U/ml (P < 0.05). Neopterin levels also showed a significant rise. M-CSF levels were correlated with clinical response in these patients. Increased production of M-CSF and the activation of mononuclear phagocytes may be involved in clinical responses to IFN-alpha in early-stage CLL.

Serum levels of macrophage colony stimulating factor (M-CSF) in liver disease

We investigated the serum level of macrophage colony stimulating factor in acute and chronic liver disease. Levels of macrophage colony stimulating factor (mean +/- SD, ng/ml) were significantly higher in acute hepatitis (5.67 +/- 1.01, p < 0.01) and chronic active hepatitis (3.34 +/- 1.19, p < 0.01) than in healthy volunteers (1.90 +/- 0.25), asymptomatic hepatitis B virus carriers (1.98 +/- 0.40), and chronic persistent hepatitis (2.34 +/- 0.43). Levels of macrophage colony stimulating factor showed a highly significant correlation with the serum alanine aminotransferase levels in acute hepatitis (p < 0.01, rs = 0.903) and in chronic active hepatis (p < 0.01, rs = 0.672). Levels of macrophage colony stimulating factor in patients with cirrhosis (cirrhosis; 3.11 +/- 0.93 and hepatocellular carcinoma; 3.30 +/- 0.74) were significantly higher than in patients with chronic persistent hepatitis although the alanine aminotransferase levels were not significantly different. In cirrhosis, levels of macrophage colony stimulating factor correlated positively with the serum alanine aminotransferase levels (p < 0.05), total bilirubin levels (p < 0.05), and indocyanine green clearance (p < 0.05). An immunohistochemical study showed an increased number of macrophage colony stimulating factor positive mononuclear cells in portal areas in acute hepatitis. Our findings suggest that; (a) the serum levels of macrophage colony stimulating factor represent ongoing hepatocellular necrosis in acute and chronic liver disease, (b) the source of the increase in the serum macrophage colony stimulating factor levels in hepatic inflammation may be, in part, its production by infiltrating mononuclear cells in the liver, and (c) cirrhosis also causes elevated serum levels of macrophage colony stimulating factor.

Timing in administration of a heat-killed Lactobacillus casei preparation for radioprotection in mice.

A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy 137Cs whole-body gamma-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice.

Establishment of radioimmunoassay for human macrophage colony-stimulating factor using recombinant human macrophage colony-stimulating factor as tracer and immunogen.

A sensitive and reliable radioimmunoassay (RIA) for human macrophage colony-stimulating factor (M-CSF) was developed using recombinant human M-CSF (rhM-CSF) as tracer and immunogen. The assay was quantitative over the range of 50 pg/ml and 5.0 ng/ml for M-CSF in human urine and serum, and more sensitive and specific than the murine bone marrow assay. The average level of human M-CSF in urine from normal males (N = 71) and females (N = 46) was 3.94 +/- 1.78 ng/ml (2.85 +/- 1.15 micrograms/g creatinine), and 3.53 +/- 1.70 ng/ml (3.31 +/- 1.12 micrograms/g creatinine), respectively. The serum levels were 1.95 +/- 0.38 ng/ml for males (N = 117), and 1.93 +/- 0.49 ng/ml for females, (N = 16). The results with the urine and sera showed that there was no difference in the M-CSF levels due to age or gender.

Serum levels of macrophage colony-stimulating factor in patients with ovarian cancer undergoing second-look laparotomy

Objective: The purpose of this study was to evaluate the prognostic significance of macrophage colony-stimulating factor serum levels in patients with ovarian cancer undergoing second-look laparotomy. Study design: The presurgical serum levels of macrophage colony-stimulating factor from 33 consecutive patients with ovarian cancer undergoing second-look laparotomy were determined and compared with those of 50 healthy control subjects. Mean differences in groups were evaluated with the Student f test. Results: Sixteen of 33 patients had a positive result at second look and a mean serum macrophage colony-stimulating factor level of 2.31 ± 1.45 ng/ml. Seventeen of 33 patients had a negative result at second look and a mean macrophage colony-stimulating factor level of 1.90 ± 0.86 ng/ml ( p > 0.05). The mean macrophage colony-stimulating factor level in the control group was 1.20 ± 0.51 ng/ml. This was statistically lower than the mean level found in patients with a negative second-look result ( p Conclusion: Regardless of tumor status, serum macrophage colony-stimulating factor levels tend to be elevated at the time of second-look laparotomy.

Serum levels of macrophage colony-stimulating factor in patients with ovarian cancer undergoing second-look laparotomy

The purpose of this study was to evaluate the prognostic significance of macrophage colony-stimulating factor serum levels in patients with ovarian cancer undergoing second-look laparotomy. The presurgical serum levels of macrophage colony-stimulating factor from 33 consecutive patients with ovarian cancer undergoing second-look laparotomy were determined and compared with those of 50 healthy control subjects. Mean differences in groups were evaluated with the Student t test. Sixteen of 33 patients had a positive result at second look and a mean serum macrophage colony-stimulating factor level of 2.31 +/- 1.45 ng/ml. Seventeen of 33 patients had a negative result at second look and a mean macrophage colony-stimulating factor level of 1.90 +/- 0.86 ng/ml (p greater than 0.05). The mean macrophage colony-stimulating factor level in the control group was 1.20 +/- 0.51 ng/ml. This was statistically lower than the mean level found in patients with a negative second-look result (p less than 0.05). Regardless of tumor status, serum macrophage colony-stimulating factor levels tend to be elevated at the time of second-look laparotomy.

Changes in hemopoietic and regulator levels in mice during fatal or nonfatal malarial infections: II. Nonerythroid populations

Levels of mature lymphocytes, granulocytes, macrophages, platelets, their progenitor cells, and cytokines were monitored in the blood, marrow, and spleen during fatal or nonfatal murine malarial infections. In all four malaria models, before anemia developed, there was a lymphopenia, a rapid lymphocyte depletion in the marrow with a compensating rise in spleen lymphocytes, thrombocytopenia with increased megakaryocytic progenitor cell numbers, and monocyte increases in the bone marrow and later the spleen. The development of anemia was associated with a monocytosis and neutropenia, an increase in granulomonocytic progenitor cells in the spleen, and a reduction of spleen lymphocytes. Spleen granulocytes, monocytes, and their progenitor cells increased two- to threefold more in nonfatal than in fatal malaria and the spleen lymphocyte pool became severely depleted in fatal malaria. The data suggest that a defective effector cell response was of importance for the fatal outcome of the disease. Other than an early rise in serum macrophage colony stimulating factor levels in fatal infections, changes in levels of the regulators of these effector cells did not correlate well with the outcome of the infection.

Effect of acute nutritional deprivation on macrophage colony-stimulating factor and macrophage progenitor cells in mice.

The effect of short-term nutritional deprivation on host defenses and on the parameters of macrophage production was determined in outbred mice. Confirming previous data from this laboratory, initial experiments demonstrated that starved mice were relatively resistant to infection by Listeria monocytogenes as determined by spleen and liver bacterial counts. The number of macrophage progenitor cells in bone marrow rose slightly during a 72-h starvation period and returned to normal during refeeding. By contrast, the number of progenitor cells in spleens fell to 12% of the base line during starvation. The concentration of the macrophage colony-stimulating factor in serum decreased during starvation and returned to normal during refeeding. Additional experiments were performed to determine whether starved mice had increased parameters of macrophage production during listerial infection. The number of progenitor cells in the bone marrow and spleens of starved mice had increased compared with that of fed mice early in infection. Macrophage colony-stimulating factor levels in starved mice rose early and remained elevated during infection but were not as high as in fed mice. These data document the changes in the parameters of monocyte production during starvation and suggest that the number of macrophage progenitor cells may be related to increased resistance to L. monocytogenes.

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.