Elevated Granulocyte Colony-stimulating Factor Levels Research Articles

Elevated granulocyte-colony stimulating factor and hematopoietic stem cell mobilization in Niemann-Pick type C1 disease

Niemann-Pick type C1 (NPC1) disease is a progressive lysosomal storage disorder caused by mutations of the NPC1 gene. While neurodegeneration is the most severe symptom, a large proportion of NPC1 patients also present with splenomegaly, which has been attributed to cholesterol and glycosphingolipid accumulation in late endosomes and lysosomes. However, recent data also reveal an increase in the inflammatory monocyte subset in the Npc1nih mouse model expressing an Npc1 null allele. We evaluated the contribution of hematopoietic cells to splenomegaly in NPC1 disease under conditions of hypercholesterolemia. We transplanted Npc1nih (Npc1 null mutation) or Npc1wt bone marrow (BM) into Ldlr−/− mice and fed these mice a cholesterol-rich Western-type diet. At 9 weeks after BM transplant, on a chow diet, the Npc1 null mutation increased plasma granulocyte-colony stimulating factor (G-CSF) by 2-fold and caused mild neutrophilia. At 18 weeks after BM transplant, including 9 weeks of Western-type diet feeding, the Npc1 mutation increased G-csf mRNA levels by ∼5-fold in splenic monocytes/macrophages accompanied by a ∼4-fold increase in splenic neutrophils compared with controls. We also observed ∼5-fold increased long-term and short-term hematopoietic stem cells (HSCs) in the spleen, and a ∼30–75% decrease of these populations in BM, reflecting HSC mobilization, presumably downstream of elevated G-CSF. In line with these data, four patients with NPC1 disease showed higher plasma G-CSF compared with age-matched and gender-matched healthy controls. In conclusion, we show elevated G-CSF levels and HSC mobilization in the setting of an Npc1 null mutation and propose that this contributes to splenomegaly in patients with NPC1 disease.

Elevated Granulocyte Colony-stimulating Factor Levels in Patients With Active Phase of Adult-onset Still Disease.

Neutrophilia is a hallmark of adult-onset Still disease (AOSD). We aimed to investigate the levels of granulocyte colony-stimulating factor (G-CSF), an essential regulator of neutrophil production and function, in the pathogenesis of AOSD. Sera were collected from 70 patients with AOSD and 20 healthy controls (HCs). The levels of G-CSF were determined by ELISA. Low-density granulocytes (LDGs) were quantified by flow cytometry. Correlations between G-CSF levels and disease activity, laboratory variables, and LDG levels in patients with AOSD were analyzed by Spearman correlation test. Patients with active AOSD presented significantly higher levels of G-CSF compared to inactive AOSD patients (P < 0.001) and HCs (P < 0.0001). The G-CSF levels were significantly decreased after active AOSD patients achieved disease remission (P = 0.0015). The G-CSF levels were significantly correlated with C-reactive protein, erythrocyte sedimentation rate, ferritin, and systemic score in AOSD (P < 0.0001). Significant correlations between the levels of G-CSF and circulating neutrophils (P < 0.0001), neutrophil-to-lymphocyte ratio (P < 0.0001), percentages of LDGs in the peripheral blood mononuclear cells (P = 0.004), as well as absolute numbers of circulating LDGs (P = 0.018) were identified. Patients with fever, evanescent rash, sore throat, arthralgia, myalgia, lymphadenopathy, or hepatomegaly/elevated liver enzymes displayed significantly higher levels of G-CSF compared to patients without these manifestations (P < 0.05). Our findings indicate that G-CSF is implicated in the pathogenesis of AOSD, and targeting G-CSF may have therapeutic potential for AOSD. In addition, introducing circulating G-CSF levels into the clinical assessment system may help to monitor disease activity.

Thermal injury of the skin induces G-CSF-dependent attenuation of EPO-mediated STAT signaling and erythroid differentiation arrest in mice

Inflammation-mediated impairment of erythropoiesis plays a central role in the development of the anemia of critical illness (ACI). ACI develops despite elevation of endogenous erythropoietin (EPO), does not respond to exogenous erythropoietin (EPO) supplementation, and contributes significantly to transfusion requirements in burned patients. We have reported previously that the reduction of red blood cell mass in the bone marrow of a burn-injured ACI mouse model is granulocyte colony-stimulating factor (G-CSF) dependent. Given that elevated G-CSF levels also have been associated with lower hemoglobin levels and increased transfusion requirements in trauma victims, we postulated that G-CSF mediates postburn EPO resistance. In ACI mice, we found that bone marrow erythroid differentiation, viability, and proliferation are impaired after thermal injury of the skin. These changes in the marrow were associated with attenuated phosphorylation of known EPO-responsive signaling nodes, signal transducer and activator of transcription 5 (STAT5) Y694 and STAT3 S727, in bone marrow erythroid cells and developed despite highly elevated levels of endogenous EPO. Severely blunted STAT5 Y694 phosphorylation in bone marrow erythroid cells after exogenous EPO supplementation confirmed that EPO signaling was impaired in ACI mice. Importantly, parenteral administration of anti-G-CSF largely rescued postburn bone marrow erythroid differentiation arrest and EPO signaling in erythroid cells. Together, these data provide strong evidence for a role for G-CSF in the development of ACI after burn injury through suppression of EPO signaling in bone marrow erythroid cells.

Dedifferentiated liposarcoma can induce a leukemoid reaction

Summary Liposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence.

The Irritation of House Dust: DEHP Heightens Inflammatory Response in Allergy Sufferers

Past research has suggested that di(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, contributes to asthma symptoms in children [EHP 116:98–103 (2008)] and to dermatitis caused by dust mite allergens in mice [EHP 114:1266–1268 (2006)]. Both the prevalence of allergic diseases and environmental exposure to phthalates have increased dramatically in the past several decades, but few studies have examined how people’s mucosal airways respond to inhaled DEHP. A new study reveals that exposure to DEHP in house dust altered the response of nasal mucosa in allergic people but not in nonallergic people [EHP 116:1487–1493; Deutschle et al.]. DEHP is found in polyvinyl chloride pipes, flooring, food containers, and other household products. Oral intake is the main route of exposure, but inhalation offers an alternative route. DEHP vaporizes from consumer products directly into the home and attaches to inhalable airborne dust particles. The subjects included 16 controls and 16 people who were allergic to house dust mites. The researchers exposed the subjects to one of two house dust samples—vacuumed samples containing 0.41 mg/g (DEHPlow) or augmented samples containing 2.09 mg/g (DEHPhigh)—for 3 hours. Nasal fluid was collected after exposure to measure biomarkers of allergic inflammation, including interleukin (IL)-2, -4, -5, -6, and -8, granulocyte colony–stimulating factor (G-CSF), and eosinophilic cationic protein (ECP). The expression of 1,232 genes was analyzed by microarrays in biopsies obtained from one nostril. Following either DEHP dose, the nonallergic group experienced no changes in nasal mucosa, and biomarker levels did not change significantly. However, DEHP exposure was associated with biomarker changes in the allergic group: half the allergic subjects challenged with DEHPlow showed significantly elevated levels of G-CSF, ECP, IL-5, and IL-6, whereas other allergic subjects exposed to DEHPhigh showed significantly diminished levels of G-CSF and IL-6, suggesting a reduced immune response. DEHP is a known modulator of gene expression, as illustrated by the current study results. Among healthy subjects, between the two exposure groups, 6 genes were upregulated and 4 were down-regulated. Among allergic subjects, between the two exposure groups, 8 genes were upregulated and 8 were downregulated. One of the genes elevated by DEHP was anti-Mullerian hormone, which is associated with proper gonad development in males. DEHP dampened the expression of lactate dehydrogenase A and fibroblast growth factor 9, regulators of testis formation. Although the gene expression data shed little light on allergic reactions, they support earlier evidence for phthalates’ action as endocrine disruptors that can impair reproductive tract development.

Elevated granulocyte colony-stimulating factor levels predict treatment failure in patients with Kawasaki disease

Kawasaki disease (KD) is an acute vasculitis in young children, frequently associated with coronary artery aneurysms. The intravenous infusion of high-dose IgG (IVIG) effectively reduces the systemic inflammation and the incidence of coronary artery lesions, although the precise underlying mechanisms are unknown. We performed expression profiling of whole blood cells to investigate the mechanisms underlying the effect of IVIG and to identify biomarkers associated with unresponsiveness to IVIG. We compared the transcript abundance among pre-IVIG and post-IVIG patients and febrile control patients. Then we analyzed the mRNA levels and the protein levels among the different cohort of patients with KD who were either responsive or nonresponsive to the initial IVIG. A total of 298 transcripts were overrepresented or underrepresented in the pre-IVIG patients compared with post-IVIG patients and febrile controls, of which 15 transcripts were differentially expressed in nonresponsive patients with KD compared with responsive patients before IVIG. The protein levels of polycythemia rubra vera 1, which was one of the most variably expressed transcripts in pre-IVIG patients, and the serum granulocyte colony-stimulating factor levels were significantly higher in nonresponsive patients than in responsive patients before the initial IVIG administration. These findings suggest that the variable gene expression profiles were correlated to the responses of patients with KD to IVIG administration. Polycythemia rubra vera 1 and granulocyte colony-stimulating factor levels may be good biomarkers for predicting response to IVIG in patients with KD.

Granulocyte colony‐stimulating factor‐induced Sweet syndrome in a healthy donor

We present the case of a 29-year-old healthy woman as a donor for peripheral blood stem cell harvest with a complication of granulocyte colony-stimulating factor (G-CSF)-induced Sweet syndrome. Four days after commencing G-CSF 10 lg/kg/d, the donor developed tender, exudative erythematous plaques on the nape of the neck, trunk and upper limbs and felt general fatigue. A biopsy specimen showed dense neutrophilic infiltrates in superficial dermis with scattered lymphocytes and histiocytes. After cessation of G-CSF, the donor was treated with oral prednisolone 30 mg for 3 days, 20 mg for 2 days and 10 mg for 2 days, with satisfactory improvement. Cases of G-CSF-induced Sweet syndrome have been described as a complication of haematological malignancies. This is the first case to be reported in a healthy person. Sweet syndrome is characterised by peripheral neutrophilic leucocytosis and acute painful papules, plaques or nodules with histological findings of dense neutrophilic infiltrates in the superficial dermis. Elevated levels of G-CSF have been shown in patients with the active phase of Sweet syndrome. G-CSF is therefore believed to be involved in the development of this syndrome. Haematologists and dermatologists should be aware that G-CSF-induced Sweet syndrome can develop in healthy donors.

Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of sweet syndrome and patients with active behcet disease: implication in neutrophil apoptosis dysfunction.

Sweet syndrome (SS), an acute inflammatory disease, has clinical and laboratory features similar to those of Behçet disease (BD). Serum levels of granulocyte colony-stimulating factor (G-CSF) are elevated in patients with SS, and exogenous administration of G-CSF has repeatedly been implicated in the causation of SS. Granulocyte colony-stimulating factor is a hematopoietic growth factor that regulates the production and differentiation of neutrophils. To clarify the role of elevated serum G-CSF levels in patients with active SS and active BD compared with those with inactive SS or BD and healthy controls. To then analyze neutrophil apoptosis in the active state of SS and BD; and to also investigate the influence of autologous serum on neutrophil apoptosis. Serum G-CSF was examined in 5 patients with active SS, 7 with inactive SS, 7 with active BD, 9 with inactive BD, and 5 healthy controls by means of an enzyme immunoassay kit. We measured apoptotic cells in the neutrophil fraction of peripheral blood collections in patients with active diseases and controls by means of flow cytometry. Serum G-CSF level was significantly higher in patients with active SS than in those with inactive SS. The difference in serum G-CSF levels among patients with active and inactive BD was also significant. Serum G-CSF level was significantly higher in patients with active SS than in those with active BD. Neutrophil apoptosis was significantly higher in patients with active SS than healthy controls. This increased apoptosis rate was also seen in patients with active BD. The increased rate of neutrophil apoptosis was significantly suppressed when the neutrophils were cultured for 18 hours in the presence of autologous active SS serum. Similarly, neutrophil apoptosis was suppressed in the presence of autologous serum in patients with active BD, but not significantly so. These findings indicate that increased production of G-CSF in patients with SS and BD may play an important role in the manifestation of these disorders. Given the suppression of neutrophil apoptosis in the active state in the presence of the influence of autologous serum, which includes elevated G-CSF level, we propose that serum G-CSF plays a significant role in the suppression of neutrophil apoptosis. Furthermore, G-CSF-induced suppression of neutrophil apoptosis appears to be deeply involved in the pathogenesis of SS and BD.

Establishment of a large cell lung cancer cell line (Y-ML-1B) producing granulocyte colony-stimulating factor

We established a new lung cancer cell line, designated Y-ML-1B, from a lung cancer of a 70-year-old Japanese man with leukocytosis and thrombocytosis. Before surgical resection, the white blood cell and platelet counts were elevated to 34,400/mm 3 and 668,000/mm 3, respectively, and the granulocyte colony-stimulating factor (G-CSF) level in the serum was increased at 141 pg/mL. The primary tumor showed an undifferentiated morphology with large cells and induced extensive thickening of the pleura in the right hemithorax. The Y-ML-1B cells grow as a monolayer, with a doubling time of 19 hours, and are tumorigenic in nude mice, which showed a morphology similar to the primary tumor in xenografts. Analysis of the supernatant of cell culture medium of Y-ML-1B showed elevated levels of G-CSF and other cytokines such as interleukin (IL)-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF), consistent with the high levels detected in the patient's serum. Cytogenetic analysis revealed aneuploidy of greater than 56 in metaphases with many structural abnormalities. Mutation analysis of the tumor suppressor genes showed that Y-ML-1B is inactivated in TP53 and RASSF1A, but not in p14 ARF, p16 INK4A, or RB. Neither activating mutations of KRAS or NRAS nor amplification of MYC or MDM2 were detected. Y-ML-1B expressed N-cadherin but not E-cadherin. This newly established cell line might serve as a useful model for studying the molecular pathogenesis for large cell cancers of the lung which express high levels of cytokines.

Low Fcγ receptor III and high granulocyte colony-stimulating factor serum levels correlate with the risk of infection in neutropenia due to Felty’s syndrome or systemic lupus erythematosus

PurposeTo determine whether serum levels of soluble Fcγ receptor III and granulocyte colony-stimulating factor (G-CSF) are associated with the risk of infection in patients with neutropenia due to Felty’s syndrome or systemic lupus erythematosus. Subjects and methodsSerum levels of G-CSF and soluble Fcγ receptor III were measured by enzyme-linked immunosorbent assays in 13 patients with neutropenia due to Felty’s syndrome, 10 patients with neutropenia due to systemic lupus erythematosus, and 41 controls with normal leukocyte counts (25 with systemic lupus erythematosus, 16 with rheumatoid arthritis). We calculated the area under the receiver operating characteristic (ROC) curves for the absolute neutrophil count, soluble Fcγ receptor III levels, and G-CSF levels. ResultsNine of the neutropenic patients (7 with Felty’s syndrome, 2 with lupus) had one or more infections within 3 months before and after blood samples were obtained. Absolute neutrophil counts were similar in neutropenic patients who did or did not have infections. However, the median level of soluble Fcγ receptor III (63 vs. 126 arbitrary units, P = 0.005) was significantly lower among patients who developed infections, whereas the median level of G-CSF (90.9 vs. 53.3 pg/mL, P = 0.04) was significantly higher compared with patients without infections. The area under the ROC curve was 0.58 (P = 0.49) for the absolute neutrophil count, 0.84 (P = 0.007) for soluble Fcγ receptor III levels, and 0.73 (P = 0.03) for G-CSF levels. ConclusionIn patients with chronic neutropenia due to rheumatic diseases, low soluble Fcγ receptor III levels and elevated G-CSF levels are better indicators of the risk of infection than is the neutrophil count.

Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo

BACKGROUND Granulocyte-colony stimulating factor (G-CSF) is a potent stimulator of granulocytopoiesis and granulocyte function. It has been used in the treatment of children with neutropenic infection; in this context, it was expected to shorten aplasia and limit the severity of infection. Clinical trials, however, have demonstrated conflicting results as to whether these aims can be met. Recently, the use of other, less lineage specific growth factors, such as interleukin (IL)-11 and stem cell factor (SCF), has also been discussed. The dynamics of growth factors and growth factor–regulating proteins during neutropenic infection, particularily in youngsters, are not well understood. METHODS Serial blood samples from children and adolescents with infection during chemotherapy-induced neutropenia were assayed for C-reactive protein, white blood cell count, IL-11, SCF, G-CSF, IL-10, IL-4, IL-1α, and IL-1β. RESULTS Although no correlation could be demonstrated between endogenous IL-11 or SCF levels, infection, and leukocyte counts, endogenous G-CSF levels were increased during both aplasia and infection. However, only the additive effects of infection and neutropenia led to maximally stimulated endogenous G-CSF levels. CONCLUSIONS The elevated G-CSF levels in a majority of patients during severe neutropenic infection may explain why a therapeutic benefit of G-CSF treatment cannot be demonstrated in all cases. There remains, however, a subgroup of patients in whom infection and cytopenia do not yield a good G-CSF response. This latter group should be identified, because they might derive some benefit from adjuvant growth factor therapy. The authors predict that the efficacy of G-CSF in the treatment of patients with neutropenic fever might depend on each individual's ability to initiate the necessary cytokine production. Cancer 1999;86:340–8. © 1999 American Cancer Society.

Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo

Granulocyte-colony stimulating factor (G-CSF) is a potent stimulator of granulocytopoiesis and granulocyte function. It has been used in the treatment of children with neutropenic infection; in this context, it was expected to shorten aplasia and limit the severity of infection. Clinical trials, however, have demonstrated conflicting results as to whether these aims can be met. Recently, the use of other, less lineage specific growth factors, such as interleukin (IL)-11 and stem cell factor (SCF), has also been discussed. The dynamics of growth factors and growth factor-regulating proteins during neutropenic infection, particularly in youngsters, are not well understood. Serial blood samples from children and adolescents with infection during chemotherapy-induced neutropenia were assayed for C-reactive protein, white blood cell count, IL-11, SCF, G-CSF, IL-10, IL-4, IL-lalpha, and IL-1beta. Although no correlation could be demonstrated between endogenous IL-11 or SCF levels, infection, and leukocyte counts, endogenous G-CSF levels were increased during both aplasia and infection. However, only the additive effects of infection and neutropenia led to maximally stimulated endogenous G-CSF levels. The elevated G-CSF levels in a majority of patients during severe neutropenic infection may explain why a therapeutic benefit of G-CSF treatment cannot be demonstrated in all cases. There remains, however, a subgroup of patients in whom infection and cytopenia do not yield a good G-CSF response. This latter group should be identified, because they might derive some benefit from adjuvant growth factor therapy. The authors predict that the efficacy of G-CSF in the treatment of patients with neutropenic fever might depend on each individual's ability to initiate the necessary cytokine production.

Serum G-CSF levels are not increased in patients with antibody-induced neutropenia unless they are suffering from infectious diseases.

By the use of a G-CSF-specific ELISA we determined the serum granulocyte-colony stimulating factor (G-CSF) levels in 63 patients with antibody-induced neutropenia including neonatal immune neutropenia, autoimmune neutropenia, and drug-induced immune neutropenia. In the sera of 20 patients, elevated G-CSF levels of 60-1006 pg/ml (normal <39 pg/ml) were observed. These patients suffered from infectious diseases at the time of blood collection. G-CSF levels normalized after successful antibiotic treatment, indicating that increased G-CSF production in patients with immune neutropenia may be primarily the result of infection and not of neutropenia.

Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.

To determine the mechanisms that lead to the decrease in bone marrow production of neutrophils during burn sepsis. Impaired bone marrow granulopoiesis during burn sepsis often results in neutropenia despite elevated circulating levels of granulocyte colony-stimulating factor (G-CSF). To date, neither the specific stages of neutrophil maturation involved in the bone marrow suppression nor the mechanisms for the impairment have been determined. Peripheral blood absolute neutrophil count and G-CSF levels were determined in mice 3 days after randomization to control, burn alone, or burn plus a topical inoculation of Pseudomonas aeruginosa (1000 colony-forming units). Bone marrow aspirates were analyzed for their neutrophil differentiation patterns by Gr-1 antigen expression and their G-CSF receptor status. Histologic analysis of liver, lung, spleen, and wound site was performed. In burn sepsis, absolute neutrophil count was reduced whereas plasma G-CSF levels were elevated, and myeloid differentiation was significantly shifted toward the immature mitotic myeloid cells. Bone marrow G-CSF receptor mRNA levels and G-CSF-stimulated proliferation were substantially decreased in burn sepsis. Histologic analysis revealed no significant neutrophil infiltration into the tissues. In thermal injury with superimposed sepsis, neutropenia and myeloid maturation arrest, despite the elevated levels of G-CSF, correlate with the reduction in bone marrow G-CSF receptor expression. These observations may provide a potential mechanism for neutropenia in sepsis.

Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections.

To investigate the physiological role of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adaptation mechanisms of myelopoiesis to enhanced demand, we studied both cytokines and their myeloid target cells in hematologically healthy patients suffering from acute bacterial infections. Endogenous serum levels of G-CSF and GM-CSF, granulocyte-macrophage colony-forming cell (GM-CFC) concentrations, and differential counts were determined for the peripheral blood of 57 patients with clinically apparent bacterial infections (26 males and 31 females aged 16 to 89 years) and 18 healthy controls (8 males and 10 females aged 23 to 84 years). Patients were selected for acute-phase protein and at least two additional clinical signs reflecting a bacterial infection. Patients showed significantly higher numbers of myeloid progenitor cells than controls (median, 68 versus 26 GM-CFC/ml; P < or = 0.01). G-CSF but not GM-CSF levels were found to be elevated (> or = 50 to 863 pg/ml). In the acute stage of infection, progenitor and cytokine levels were not influenced by gender, differences in therapy, or localization of the infection. Progenitor and G-CSF levels were not associated with absolute neutrophil counts or C-reactive protein. However, a negative correlation between number of GM-CFC per milliliter and age (R = -0.47; P < or = 0.001) and an inverse relationship between the incidence of high GM-CFC concentrations and elevated G-CSF levels (phi = -0.34; P < or = 0.01) were found. Combining both parameters into a cytokine-progenitor pattern, we observed a highly significant age-dependent response of myelopoiesis to inflammation (P < or = 0.001). Younger patients had high progenitor counts (> 75 GM-CFC/ml) associated with G-CSF levels below 50 pg/ml, whereas for the older patients, the reverse pattern was predominant. The results indicate that the age-dependent myelopoietic response to acute bacterial infections is characterized by an inverse relationship between progenitor cells and G-CSF. The observed cytokine-progenitor patterns could have implications for therapy with G-CSF and the prognosis of infectious diseases.

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research, Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the χ2 test (p <0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.