Serum Granulocyte-macrophage Colony-stimulating Factor Levels Research Articles

Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a syndrome that results from the accumulation of lipoproteinaceous material in the alveolar space. According to the underlying pathogenetic mechanisms, three different forms have been identified, namely primary, secondary and congenital. Primary PAP is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling due to the presence of neutralising autoantibodies (autoimmune PAP) or GM-CSF receptor genetic defects (hereditary PAP), which results in dysfunctional alveolar macrophages with reduced phagocytic clearance of particles, cholesterol and surfactant. The serum level of GM-CSF autoantibody is the only disease-specific biomarker of autoimmune PAP, although it does not correlate with disease severity. In PAP patients with normal serum GM-CSF autoantibody levels, elevated serum GM-CSF levels is highly suspicious for hereditary PAP. Several biomarkers have been correlated with disease severity, although they are not specific for PAP. These include lactate dehydrogenase, cytokeratin 19 fragment 21.1, carcinoembryonic antigen, neuron-specific enolase, surfactant proteins, Krebs von Lungen 6, chitinase-3-like protein 1 and monocyte chemotactic proteins. Finally, increased awareness of the disease mechanisms has led to the development of pathogenesis-based treatments, such as GM-CSF augmentation and cholesterol-targeting therapies.

Can serum granulocyte-macrophage colony-stimulating factor and CCL17 levels be a marker of disease activation in spondyloarthritis?

The aim of this cross-sectional study was to investigate if serum levels of granulocytemacrophage colony-stimulating factor (GM-CSF) and CC chemokine ligand 17 (CCL17) correlate with disease activity in axial spondyloarthritis (axSpA) and peripheral spondyloarthritis (pSpA) patients. The cross-sectional study was conducted with 80 individuals (48 females, 32 males; mean age: 47.7±11.5) between March 2021 and September 2021. Of the participants, 20 were axSpA, 20 were pSpA, and 20 were active rheumatoid arthritis patients, and the remaining 20 were healthy controls. Age, sex, body mass index, disease duration, comorbid diseases, smoking status, medical treatments, C-reactive protein (CRP) level and human leukocyte antigen B27 (HLA-B27) positivity were recorded. Serum GM-CSF and CCL17 levels were analyzed by ELISA. Ankylosing Spondylitis Disease Activity Score with CRP (ASDAS-CRP) was used to evaluate the disease activity of patients with spondyloarthritis. Functional status of spondyloarthritis patients was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI). While the serum GM-CSF levels were similar in the axSpA and pSpA groups, they were significantly higher than the healthy control group (p=0.021 and p=0.009, respectively). There was a significant correlation between GM-CSF levels and ASDAS-CRP (r=0.545, p=0.013) and BASFI (r=0.546, p=0.013) in the axSpA group. In active axSpA patients, the cut-off value for GM-CSF was 15.89 pg/mL (sensitivity 50%, specificity 100%). No differences were detected in serum CCL17 levels among the groups. The results suggest that serum GM-CSF levels may be used as a new marker for the evaluation of disease activity in axSpA, and GM-CSF might be a therapeutic target.

Impact of persistent antigenic challenges and splenectomy on immune cells in β-Thalassemic patients.

Infection is common in thalassemia patients and is one of the leading causes of death. It's still unclear why these individuals are so sensitive to infection. There is strong evidence that a deficiency in the functioning of phagocytic cells plays a key role in the weakened resistance to pathogenic bacteria. The purpose of this study was to investigate the function of phagocytic cells by comparing the serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and Neopterin in thalassemia patients to healthy people. The study included 50 thalassemia patients and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was applied to estimate the serum levels of GM-CSF and Neopterin. Serum levels of GM-CSF were significantly elevated in thalassemia patients when compared to healthy people (p < 0.05), while serum levels of Neopterin showed no significant change between thalassemia patients and healthy controls. Both serum levels of GM-CSF and Neopterin showed no significant difference between Splenectomized and healthy controls. Total leukocyte counts, lymphocytes, MID (monocytes), platelets, and RBC were all significantly higher in thalassemia patients compared to healthy controls. But, granulocyte counts showed no significant difference between the thalassemia patients and the healthy controls. On the other hand, total leukocytes, monocytes, lymphocytes and platelets counts were significantly raised in splenectomized patients when compared to healthy controls and non-splenectomized patients, respectively. We came to the conclusion that thalassemia patients have a high immune cell count, which is most likely due to the antigenic difficulties posed by blood transfusions. On the other hand, these patients have an impaired immune system.

Serum granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in patients with active radiographic axial spondyloarthritis and persists despite anti-TNF treatment

BackgroundAccumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment.MethodsPatients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4–6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1).ResultsTwelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7, which decreased to 4.1±1.7 and 2.2±0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other.ConclusionsGM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA.

Initial serum GM-CSF levels are associated with the severity of cerebral small vessel disease in microscopic polyangiitis patients

Serum cytokine levels were comprehensively measured, and the association with cerebrovascular lesions on brain magnetic resonance imaging (MRI) in microscopic polyangiitis (MPA) patients was investigated. The initial serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were significantly higher in the high-grade white matter hyperintensities (WMH) group than those in the low-grade WMH group. In multivariate analyses, high serum levels of GM-CSF were independently associated with high-grade WMH. The initial serum GM-CSF levels correlated positively with the Birmingham Vasculitis Activity Score and semi-quantitative scales of WMH. The initial serum GM-CSF levels were associated with the severity of WMH in MPA patients.

Assessment of molecular response after tyrosine kinase inhibitors & serum granulocyte-macrophage colony-stimulating factor levels in Egyptian patients with chronic myelogenous leukemia in chronic phase

BackgroundIn chronic myelogenous leukemia (CML), one of the most important & documented benefits of the profitable use of tyrosine kinase inhibitors (TKIs) is achieving major molecular response (MMR) & undoubtedly raising the life expectancy. We evaluate the molecular response after one year of 32 newly diagnosed Egyptian CML patients in chronic phase receiving TKIs (imatinib vs nilotinib). Quantitative assessment of BCR-ABL1 mRNA transcripts using real-time reverse transcription polymerase chain reaction was done. Also, baseline quantitative detection of serum GM-CSF level was done using enzyme linked immunosorbent assays technique together with correlation to molecular response. ResultsThirty-two patients were included in the study, but the molecular response was assessed in only 17 patients; 6 patients were under imatinib treatment and 11 patients received nilotinib. Overall within 1 year, 7/17 (41.2%) patients achieved major molecular response (MMR) with median BCR-ABL1 level of 0.06% on the international scale (IS). Five patients (29.4%) reached MR4 with median BCR-ABL1 level 0.007% on IS. Regarding TKIs therapy, each MMR and MR4 was noticed in 2/6 (33.3%) patients who received imatinib treatment with median BCR-ABL1 level of 0.01% & 0.005% on the IS, respectively. However, MMR and MR4 were detected in 5/11 (45.4%) & 3/11 (27.3%) patients who received nilotinib treatment, respectively with median BCR-ABL1 level 0.06% & 0.008% on the IS, respectively. Median serum GM-CSF level was higher in patients who reached MR4 than patients who achieved MMR but it did not reach significant difference (p value = 0.7). ConclusionThis study demonstrates the molecular profile of Egyptian CML patients after TKIs treatment. Also, it assesses the baseline serum GM-CSF levels to predict therapeutic outcome in CML patients.

Role of Innate Immunity in Patients with HBV Infection

Background: The hepatitis B virus [HBV] is an infectious disease and its one of the great public health problem, its outcome depends on the kinetics of the virus-host interaction and specifically on the strength of the innate and adaptive, humoral and cellular immune response. Thus interactions between the virus and the components of immune systems plays an important role in the pathogenesis of the disease. This study aimed to evaluate innate immune response in different clinical courses of HBV infection by estimation serum levels of granulocytemacrophagecolony stimulating factor (GM-CSF), Interleukin-1 (IL-1 ), Interleukin-8 (IL-8 ) , immunoglobulin A (IgA), IgM, IgG and Complement component (C3and C4) levels. Aim of study: to evaluate role of immune response in clinical course of hepatitis B infection Patients and Method: This study based on 78 patients with HBV infection attending the Public Health Laboratories. Their ages ranged from (14-65) years, (58 males and 20 females) compared with 20 healthy subjects (12 males and 8 females) as control group. This study extended from first of January 2015 to first of January 2017. The patients were classified to three groups on the bases of serologic markers (HBsAg, HBe Ag, HBc Ab IgM) according to WHO department of communicable disease surveillances and response, liver function tests which are used as supportive indicator for the liver injury, history of the illness, and full clinical assessment. The first group includes twenty-eight patients with acute HBV infection, second group include twenty cases identified as chronic healthy HBsAg carriers group and the last third group include thirty cases of chronic HBV group Results: By using enzyme immuno assay [ELISA] technique, serum levels of interleukin1alpha [IL-1α], interleukin-8 [IL-8], and granulocyte-macrophage-colony stimulating factor [GM-CSF] were measured in all patients compared to that of healthy control group. The mean levels of IL-1α and IL-8 showed a significant increase in serum of patients with newly infected (acute) HBV and chronic HBV compared with studied control group [P=0.04 and P=0.001 respectivel]. However, the mean serum levels for IL-1α and IL-8 recorded a non significant increase in patients with chronic healthy HBsAg carriers [P=0.17 and P=0.4 respectively]. While the mean serum levels of GM-CSF showed a significant rise in acute HBV only [P=0.01]. Moreover, serum immunoglobulins [IgG, IgM, IgA] and complement component [C3, C4] levels also evaluated by using single radial immunodiffusion test (SRID). The mean serum IgA, IgG and IgM levels showed a significant increase in chronic HBV group as compared to that of control group [ P=0.000 ,P=0.000 and P=0.001 respectively].. The mean serum C3 and C4 levels showed a significant lower serum level in all groups compared to control studied group [P=0.000]. Conclusion: this data demonstrate that immunological differences do exist between different clinical groups with HBV infection and may reflect the role of the innate immune system in host defense and disease

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans.

Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

Cytokine profiling reveals increased serum inflammatory cytokines in idiopathic choroidal neovascularization

BackgroundThe exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity.MethodsThis case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF).ResultsSerum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area.ConclusionSerum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.

Comparing of pro-inflammatory cytokines in the woman with preterm and term labors

Background: Preterm birth is one of the most important issues in obstetrics medicine and yet, the leading cause of morbidity and long-term disabilities such as neuro developmental impairments. There have been many studies trying to recognize responsible factors and develop new methods to predict and cure the condition. One important factor in preterm birth is immune system and immune factors such as cytokines. In this regard, we aimed to measure different cytokines in sera of mothers experiencing preterm birth.Methods and Materials: In this case control study, we measured serum levels of IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 (CXCL8), IL-10, IL-12(p70), IL-13, interferon gamma (IFN-g), granulocyte macrophage colony stimulating factor (GMC-SF) and TNF-alpha in women with preterm and term labors according to Enzyme-Linked Immune Sorbent Assay (ELISA).Results: Serum levels of IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13 and TNF-α in preterm group were significantly higher than control group (P < 0.05, for all). Also, GMC-SF serum levels in the preterm group were significantly lower than control group (P < 0.0001).Conclusion: here in this study we indicated that immune system and pro-inflammatory cytokine have been change in preterm birth and further examinations on more patients may create new insights in developing methods to predict and prevent the disease.

Characterization of Mast Cell Activation Syndrome

Mast cell (MC) activation syndrome (MCAS) is a recently recognized, heterogeneous disease of chronic multisystem inflammation (CMI) ± allergy. MCAS features aberrant MC reactivity and constitutive MC activation with little accumulation of MCs, distinct from mastocytosis [Afrin, Ann Med 48:190-201]. Whether clonality in MCAS is common is debated. Symptoms (sxs) range from mild to disabling, even life-threatening; prevalence may be as high as 17% [Molderings, PLoS One 8(9):e76241], underscoring the importance of studying MCAS. Notwithstanding case reports, small case series, and reviews to date, we report the first systematic characterization of a large MCAS cohort.Methods: Under IRB-approved (Pro00015852, Pro00015857), Mastocytosis Society-sponsored protocols at one center, charts of 298 MCAS pts accrued retrospectively ("retro," diagnosed Nov 2008 - Sep 2012), plus 115 accrued prospectively (diagnosed Apr 2012 - Oct 2013), were reviewed for demographics, comorbidities (probs), sxs, family histories (FHs), physical exam and lab findings. For purposes of follow-up (f/u), data cut-off was June 30, 2014. Data were abstracted by LBA from available records. All were diagnosed with MCAS per criteria [Molderings, J Hematol Oncol 4:10] which in our experience (>1,000 pts) reflects MCAS behavior better than other proposals [e.g., Valent, Int Arch Allergy Immunol 157:215-25]. Blood samples from prospective pts were examined by flow cytometry for clonal MC disease (co-expressing CD45 and CD117 plus CD25 and/or CD2) and tested (ELISA kits, RayBioTech (Norcross, GA)) for elevated (↑) serum levels of cytokines (monocyte colony stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3), and tumor necrosis factor alpha (TNF-α)) potentially driving the mild relative monocytosis often seen in MCAS [Afrin, Blood 122:5240]; samples for cytokine testing were kept chilled from collection through assay, including centrifugation.Results: Most of the 413 pts were female (69%) and Caucasian (75%). Median (med) ages at sx onset and diagnosis (dx) were 9 yrs (range 0-88) and 49 yrs (range 16-92). Med time from sx onset to dx was 30 years (range 1-85). Med number of probs was 11 (range 1-66). Med number of sxs was 20 (range 2-84). Med number of FH issues was 4 (range 0-33). Tables 1, 2, and 3 show pts' common clinical and lab characteristics and relative utility of various MC mediators in dx. Frequencies of clinical findings in our pts likely are underestimates due to retro assessment in 298/413 (72%). As reported before for the retro subset [Blood 122:5240], general laboratory abnormalities in these MCAS pts were common, modest, and persistent.Most of our pts (72%) appeared chronically ill at times but overall healthier than expected from their many complaints, contributing to prior dx of somatism in most. Many pts "learned to live with it," no longer reporting some sxs unless asked.In the prospective pts, flow cytometry failed to find the targeted signature of clonal MC disease. Serum M-CSF, GM-CSF, IL-3, and TNF-α levels were assessed and, despite correct negative and positive control results, were not found ↑ in any pt.As of f/u cut-off, 388 pts (94%) were alive, 1 was lost to f/u and 24 pts (6%) had died of many causes (most commonly (25%) cancer). Data were insufficient to calculate meaningful survival statistics from time of dx.Discussion: Long sx duration in MCAS - and cessation, of futility, in reporting sxs - show comprehensive history in pts with CMI is important. Routine lab abnormalities are seen long before dx but are modest and thus given short shrift by busy practitioners, but this study suggests they should spark thought of MCAS in pts with CMI and no unifying dx.Relative utilities of MC mediators for dx in our pts were similar to a recent report [Zenker, Blood 126:5174] and further suggest serum tryptase - while still a good screen for MC neoplasia - poorly reflects MC activation.Conclusions: MCAS is challenging to recognize, but its prevalence, morbidity, chronicity, and ability of most pts to identify helpful therapy merit attention to dx and treatment. Our data, characterizing MCAS more comprehensively than ever before, may facilitate its clinical recognition. More research is needed to identify etiologies (and linkages with chronic inflammatory diseases), facilitate dx, and guide therapy. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Elevated serum granulocyte-macrophage colony-stimulating factor levels during radiotherapy predict favorable outcomes in lung and esophageal cancer.

The combination of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiotherapy (RT) has been demonstrated to strengthen the antitumor immune response. We hypothesized that the variation of GM-CSF during RT was correlated with cancer prognosis. We measured serum levels of GM-CSF and interferon-γ (IFN-γ) before and during RT in 126 unresectable lung and esophageal cancer patients and performed survival analyses. Upregulated GM-CSF levels during RT correlated with longer overall survival (OS) and progression-free survival (PFS). On the other hand, no difference in OS or PFS was seen at different IFN-γ levels. However, the “integrated factor”, computed as the combination of high pre-RT IFN-γ levels and upregulated GM-CSF, correlated with prolonged OS and PFS. Multivariate analyses revealed that GM-CSF levels and the integrated factor were both stronger independent prognostic factors than disease stage. These data demonstrate that GM-CSF levels during RT can be used as a prognostic biomarker for lung and esophageal cancer.

Protective effects of paeoniflorin and albiflorin on chemotherapy-induced myelosuppression in mice

Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in traditional Chinese medicines (TCM). Two isomers, paeoniflorin (PF) and albiflorin (AF), are isolated from P. lactiflora. The present study aimed to investigate the protective effects of PF and AF on myelosuppression induced by chemotherapy in mice and to explore the underlying mechanisms. The mouse myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (CP, 200 mg·kg−1). The blood cell counts were performed. The thymus index and spleen index were also determined and bone morrow histological examination was performed. The levels of tumor necrosis factor-α (TNF-α) in serum and colony-stimulating factor (G-CSF) in plasma were measured by Enzyme-Linked Immunosorbent Assays (ELISA) and the serum levels of interleukin-3 (IL-3), granulocyte-macrophagecolony-stimulatingfactor (GM-CSF), and interleukin-6 (IL-6) were measured by radioimmunoassay (RIA). The levels of mRNA expression protein of IL-3, GM-CSF and G-CSF in spleen and bone marrow cells were determined respectively. PF and AF significantly increased the white blood cell (WBC) counts and reversed the atrophy of thymus. They also increased the serum levels of GM-CSF and IL-3 and the plasma level of G-CSF and reduced the level of TNF-α in serum. PF enhanced the mRNA level of IL-3 and AF enhanced the mRNA levels of GM-CSF and G-CSF in the spleen. PF and AF both increased the protein levels of GM-CSF and G-CSF in bone marrow cells. In conclusion, our results demonstrated that PF and AF promoted the recovery of bone marrow hemopoietic function in the mouse myelosuppression model.

Activated T cells enhance interferon-α production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes

ObjectivesPatients with systemic lupus erythematosus (SLE) have an ongoing interferon-α (IFN-α) production by plasmacytoid dendritic cells (pDCs). We investigated whether T cells can promote IFN-α production by pDCs.MethodsHuman pDCs were...

Impact of Serum Granulocyte-Macrophage Colony-Stimulating Factor Levels among Diabetes Patients in Hilla City - Iraq

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine with growth factor-like properties for monocytes and dendritic cells. Methods: Study subjects were recruited from the hospital in Hilla city. Healthy controls (n=15) and D.M. patients (n=35) were included in the study. Serum levels of GM-CSF and Anti-Insulin Antibody (AIA) measured by using ELISA technique. Results: The serum GM-CSF levels were significantly higher among diabetes subjects as compared with subjects without diabetes and results showed a high significant in serum AIA and glucose levels in patient as compare with control (p=0.009, P=0.001). The serum GM-CSF levels were increased in age group (45-54 years) shows the higher percent (42.85%) of patients with diabetes, with decreased of AIA and GM-CSF level rather than other age groups. Conclusions: There is indirect relationship between AIA and GM-CSF level and that is mean increased AIA and glucose level reflect the reduced GM-CSF level among the diabetic patients may be used as biomarker or use GM-CSF as co-therapy with insulin.

Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers

BackgroundTo evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing. MethodsWe studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. ResultsAll EPC phenotypes except the kinase insert domain receptor (KDR)+CD133+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34+KDR+ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. ConclusionsUncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34+KDR+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.

Inflammatory Biomarkers Predict Airflow Obstruction After Exposure to World Trade Center Dust

The World Trade Center (WTC) collapse on September 11, 2001, produced airflow obstruction in a majority of firefighters receiving subspecialty pulmonary evaluation (SPE) within 6.5 years post-September 11, 2001. In a cohort of 801 never smokers with normal pre-September 11, 2001, FEV1, we correlated inflammatory biomarkers and CBC counts at monitoring entry within 6 months of September 11, 2001, with a median FEV(1) at SPE (34 months; interquartile range, 25-57). Cases of airflow obstruction had FEV(1) less than the lower limit of normal (LLN) (100 of 801; 70 of 100 had serum), whereas control subjects had FEV(1) greater than or equal to LLN (153 of 801; 124 of 153 had serum). From monitoring entry to SPE years later, FEV(1) declined 12% in cases and increased 3% in control subjects. Case subjects had elevated serum macrophage derived chemokine (MDC), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor, and interferon inducible protein-10 levels. Elevated GM-CSF and MDC increased the risk for subsequent FEV(1) less than LLN by 2.5-fold (95% CI, 1.2-5.3) and 3.0-fold (95% CI, 1.4-6.1) in a logistic model adjusted for exposure, BMI, age on September 11, 2001, and polymorphonuclear neutrophils. The model had sensitivity of 38% (95% CI, 27-51) and specificity of 88% (95% CI, 80-93). Inflammatory biomarkers can be risk factors for airflow obstruction following dust and smoke exposure. Elevated serum GM-CSF and MDC levels soon after WTC exposure were associated with increased risk of airflow obstruction in subsequent years. Biomarkers of inflammation may help identify pathways producing obstruction after irritant exposure.

Increased Levels of Serum Granulocyte-Macrophage Colony-Stimulating Factor Is Associated with Activated Peripheral Dendritic Cells in Type 2 Diabetes Subjects (CURES-99)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine with growth factor-like properties for monocytes and dendritic cells (DCs). In the present study, serum GM-CSF levels and the activation status of DCs were studied in type 2 diabetes mellitus (T2DM) subjects. Study subjects were recruited from the Chennai Urban Rural Epidemiology Study. Healthy controls (n=45) and T2DM patients (n=45) were included in the study. Serum levels of GM-CSF, interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Enumeration of circulating DCs (myeloid [m] and plasmocytoid [p]) and its surface antigen expression were quantified by flow cytometry. The serum GM-CSF levels were significantly higher among diabetes subjects compared with subjects without diabetes and showed a positive correlation with glycated hemoglobin (r=0.208, P=0.018). The serum GM-CSF levels were lower in subjects on combined insulin and oral hypoglycemic agents (OHA) treatment (1.09 pg/mL) compared with those taking OHA alone (1.9 pg/mL). The increased GM-CSF levels were associated with the activated phenotype of mDCs and pDCs, as determined by up-regulation of the lineage markers. The activated state of mDCs and pDCs seen among diabetes subjects might be due to the increased levels of GM-CSF and other pro-inflammatory cytokines.

Clinical Significance of Determination of Serum CoX-2,IL-8 and GM-CSF Levels in Pediatric Patients with Bronchial Asthma

Objective To explore the changes of serum COX-2,IL-8 and GM-CSF levels in asthmatic children and their clinical significance.Methods The serum COX-2,IL-8 and GM-CSF levels of 86 asthmatic children,including 42 cases in the acute attack group and 44 cases in the remission group,and 40 healthy controls were detected by sandwich ELISA.Results The serum COX-2,IL-8 and GM-CSF levels in the asthmatic group significantly increased(P＜0.05).The serum COX-2,IL-8 and GM-CSF levels in the acute attack group were higher than those in the remission group(P＜0.05);the serum COX-2,IL-8 and GM-CSF levels in both acute attack group and remission group were higher than those in control group(P＜0.05).Conclusions These cytokines participated in the pathogenesis of bronchial asthma.Monitoring the changes of their serurm levels was helpful for the management of the diseaSes. Key words: Asthma; cyclooxygenase-2; Interleukin-8; Granulocyte-macrophage colony stimulating factor(GM-CSF); Child

Serum levels of GM-CSF 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study

Sulfur mustard (SM) is highly toxic for various organs. The eyes, skin, respiratory tract, as well hematopoietic and immune systems are the main organs affected by SM. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a potent cytokine that plays an important role in the hematopoietic and immune system. The aim of this study was to determine the serum levels of GM-CSF and its relation to blood cell count and other inflammatory cytokines 20 years after SM exposure. The association of GM-CSF with the clinical severity of pulmonary, ophthalmic and dermatologic complications has also been studied. In this historical cohort study named as Sardasht-Iran Cohort Study (SICS), 369 SM exposed male participants and 125 unexposed volunteers were studied. The serum concentrations of cytokines were measured by ELISA technique. The severity of clinical complications was graded according to the criteria verified by the Medical Committee of the Foundation of Martyr and Veterans Affairs. The serum levels of GM-CSF in the SM exposed group did not display any significant differences with the control group. Median of GM-CSF was 7.33 and 9.39 pg/ml in the SM exposed group and the controls respectively. There was a positive correlation between the serum levels of GM-CSF and the percent of eosinophils only in the exposed group. Moreover, positive correlations were found between circulating levels of GM-CSF with IL-1α, IL-1β, TNF-α and IL-6. This correlation was not observed between GM-CSF and IL-8 in both study groups. The serum levels of GM-CSF did not show any significant association with clinical complications.