OBJECTIVETo observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo.

METHODSA total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR.

RESULTSCompared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ.

CONCLUSIONSIn the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.

Animals ; Chemokine CCL3 ; analysis ; Female ; Granulocyte Colony-Stimulating Factor ; blood ; Interferon-gamma ; blood ; Interleukin-18 ; therapeutic use ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use ; Staphylococcal Infections ; drug therapy ; immunology

OBJECTIVETo evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.

METHODSSeventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.

RESULTSAfter 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.

CONCLUSIONrhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.

Animals ; Bone Marrow ; pathology ; Bone Marrow Cells ; pathology ; Gamma Rays ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoiesis ; drug effects ; Hematopoietic Stem Cells ; cytology ; Humans ; Interleukin-2 ; pharmacology ; Macaca mulatta ; Radiation Injuries ; drug therapy ; Random Allocation ; Recombinant Proteins ; therapeutic use ; Thrombopoietin ; pharmacology ; Whole-Body Irradiation

OBJECTIVETo investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).

METHODSPeripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.

RESULTSTLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).

CONCLUSIONHeparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.

CD4-Positive T-Lymphocytes ; cytology ; Cell Differentiation ; Coculture Techniques ; Dendritic Cells ; cytology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Heparin ; pharmacology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; pharmacology ; Monocytes ; cytology ; Recombinant Proteins ; pharmacology ; Toll-Like Receptor 3 ; metabolism

OBJECTIVETo investigate the effect and mechanism of high dose Vitamin B3 on granulopoiesis in normal rat.

METHODSTwenty one healthy SD rats were randomly divided into three groups: the Vitamin B3 group (Vit B3 500 mg·kg⁻¹·d⁻¹, × 7 d), the rhG-CSF group (rhG-CSF 25 μg·kg⁻¹·d⁻¹, × 7 d) and the normal saline group (2 ml/d, × 7 d). The peripheral blood cell counts were analyzed by automatic blood cell counter before (day 0) treatment, the third day (day 3) and the seventh day (day 7) after administration of drugs, respectively. The concentration of serum nicotinamide adenine dinucleotide (NAD⁺) level was measured by enzymatic cycling assay before and after drugs treatment. The expressions of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPβ, C/EBPε and NAMPT mRNA were detected by reverse transcription real-time fluorescent quantitative PCR.

RESULTSThe neutrophil counts increased significantly after 7 days of Vitamin B3 and rhG-CSF treatment compared with that of control group [(1.64 ± 0.19) × 10⁹/L, (1.88 ± 0.37)× 10⁹/L vs (0.86 ± 0.18) × 10⁹/L, P<0.01]; the level of serum NAD⁺ increased significantly [(0.96 ± 0.08) nmol/L, (0.65 ± 0.12) nmol/L vs (0.36 ± 0.15) nmol/L, P<0.01]; the expression of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPε and NAMPT mRNA in bone marrow mononuclear cells were increased significantly compared with that of control group (P<0.01).

CONCLUSIONHigh dose of Vitamin B3 may play an important role in increasing absolute neutrophil count in healthy rat under steady state, and the mechanism may be dependent on NAMPT-NAD⁺-SIRT1 signaling pathways.

Animals ; Bone Marrow Cells ; Granulocyte Colony-Stimulating Factor ; Leukocyte Count ; Neutrophils ; drug effects ; Niacinamide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins

The adhesion and polarization of T lymphocytes involved in the adhesive interaction of lymphocyte function-associated antigen 1 (LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulation in vitro on the adhesion and polarization of CD4⁺ T cells of healthy human in peripheral blood. The peripheral blood mononuclear cells were collected from 12 healthy volunteers. The CD4⁺ T cells were sorted by miniMACS. The sorted CD4⁺ T cells were incubated with rhG-CSF for 24 h, then the adhesion and polarization of CD4⁺ T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by ELISA and inverted microscope. The results showed that the percentage of adhesion CD4⁺T cells in the experimental group (rhG-CSF acting on the healthy adult volunteers) (61.9 ± 5.9)% was lower than that in the control group (healthy adult volunteers without rhG-CSF stimulation) (68.3 ± 7.3)% (P < 0.05). The percentage of polarized CD4⁺T cells in the experimental group (24.3 ± 4.3)% was also lower than that in control group (47.1 ± 5.1)% (P < 0.05). It is concluded that the adhesion and polarization of CD4⁺T lymphocytes can be inhibited after rhG-CSF stimulation.
Aged ; CD4-Positive T-Lymphocytes ; drug effects ; Cell Adhesion ; drug effects ; Cell Movement ; Cell Polarity ; drug effects ; Chemokine CXCL12 ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Humans ; In Vitro Techniques ; Intercellular Adhesion Molecule-1 ; Leukocytes, Mononuclear ; Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1 ; Middle Aged ; Recombinant Proteins

The polarization and migration of T lymphocytes involves the adhesive interaction of lymphocyte function-associated antigen 1(LFA-1) with its ligand intercellular adhesion molecule 1 (ICAM-1). This study was aimed to investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) mobilization on the polarization and migration of donor's CD4(+) T cells in peripheral blood. The peripheral blood mononuclear cells were collected from 10 healthy volunteers and 10 donors on the fifth day of mobilization with rhG-CSF. And the CD4(+)T cells were purified by miniMACS. The polarization and migration of CD4(+) T cells activated by stroma cell-derived factor -1α (SDF-1α) and ICAM-1 were detected by using inverted and confocal microscopes respectively. The results showed that the percentage of polarized CD4(+)T cells from donors(32.42 ± 4.91)% was lower than that from healthy controls(56.55 ± 5.35)% (P < 0.01), the migration velocity of CD4(+)T cells from donors (7.06 ± 1.44 µm/min) was also lower than that of healthy controls(9.05 ± 1.91 µm/min)(P < 0.01). It is concluded that the polarization and migration of CD4(+)T lymphocytes is impaired after rhG-CSF mobilization.
Adolescent ; Adult ; CD4-Positive T-Lymphocytes ; cytology ; drug effects ; Case-Control Studies ; Cell Movement ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; pharmacology ; Tissue Donors ; Young Adult

OBJECTIVETo investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats.

METHODSEighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test.

RESULTS(1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both groups; the conditions in group A were better. On PID 14, all the wounds in group A were almost healed, while a small area of raw wound with incrustation still remained in some wounds of group B. On PID 3 and 7, the wound healing rates of group A were (41 ± 5)% and (75 ± 4)%, significantly higher than those of group B [(31 ± 9)% and (71 ± 4)%, with t values respectively 10.13 and 8.06, P values below 0.001]. (2) On PID 3, the epidermal cells, endothelial cells, and Fbs in the wounds of 2 groups were sparse, with heavy infiltration of inflammatory cells. The above condition in the wounds was better in group A than in group B. On PID 7, the epidermal cells, endothelial cells, and Fbs were gradually well arranged in group A; infiltration of inflammatory cells decreased, and the condition was better than that of group B. On PID 14, the wounds of group A were completely covered by epidermis, while infiltration of inflammatory cells still remained in some wounds of group B. (3) On PID 3, 7, 14, the positive expressions of CD31 and PCNA in group A were respectively 0.275 ± 0.018, 0.345 ± 0.034, 0.305 ± 0.023; 0.406 ± 0.063, 0.223 ± 0.011, 0.045 ± 0.022. They were significantly higher than those of group B (0.222 ± 0.020, 0.229 ± 0.018, 0.197 ± 0.015; 0.324 ± 0.039, 0.162 ± 0.012, 0.018 ± 0.020, with t values from 2.281 to 9.652, P < 0.05 or P < 0.01). (4) According to the microRNAs detection and screening, as compared with group B, 18 microRNAs were up-regulated while 13 were down-regulated in the wounds of group A. (5) The results of real-time fluorescent quantitative RT-PCR had good consistency with the results of microRNAs detection. (6) Enrichment analysis of KEGG signaling pathway showed that among the 31 differentially expressed microRNAs, 4 took part in the MAPK signaling pathway, 3 took part in the Wnt signaling pathway, 1 took part in the TGF-β signaling pathway, 3 took part in the epidermal growth factor receptor signaling pathway, 2 took part in the cell cycle pathway, 5 took part in the axon guidance signaling pathway, 6 took part in the focal adhesion pathway, 3 took part in the regulation of actin cytoskeleton pathway, 1 took part in the extracellular cell matrix receptor pathway, 3 took part in the adherens junction pathway, and 1 took part in the cell adhesion molecules pathway. After disclosing the blind, it showed that the ointment with red tag was the rhGM-CSF gel and the blue one was gel vehicle.

CONCLUSIONSThe rhGM-CSF gel can promote wound healing in diabetic rats, producing significant differential microRNA expression in wounds, and they may be the target at gene post-transcriptional level of rhGM-CSF gel in promoting wound healing.

Animals ; Bacteria ; isolation & purification ; Burns ; drug therapy ; microbiology ; pathology ; Diabetes Mellitus, Experimental ; complications ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Male ; MicroRNAs ; genetics ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Recombinant Proteins ; Signal Transduction ; Wound Healing ; drug effects

OBJECTIVETo investigate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on wound healing and mammalian target of sirolimus (rapamycin) signaling pathway in rats.

METHODSFifty SD rats were divided into control group (n = 25) and treatment group (n = 25) according to the random number table. All rats were inflicted with 2 cm × 2 cm full-thickness skin wound on the back. Recombinant human GM-CSF gel (10 µg/cm(2)) was applied onto the wounds in treatment group, and the actual quantity was 1 × 10(-4) µg/cm(2). Gel vehicle (10 µg/cm(2)) without any medicine was applied onto the wounds in control group. The treatment was conducted once a day up to the day of wound healing. Five rats from two groups were sacrificed on post injury day (PID) 1, 3, 5, 7, 14 respectively to observe and determine the wound healing rate. Wound tissue samples were collected at the former 4 time points to observe the histopathological changes with HE staining, and to detect the content of GM-CSF with enzyme-linked immunosorbent assay, and the expression levels of GM-CSF, CD31, and the mTOR signal pathway associated molecules P70S6K, phosphorylated (p-) P70S6K, 4E-BP1, p-4E-BP1, mTOR, p-mTOR with Western blotting. Data were processed with t test.

RESULTS(1) Wound healing rates in control group and treatment group were close on PID 1 (t = 0.307, P > 0.05). Wound healing rate in treatment group was obviously higher than that in control group on PID 3, 5, 7, and 14 (with t values from 2.704 to 4.030, P < 0.05 or P < 0.01). (2) Compared with those in control group, more abundant granulation tissue was observed in treatment group, in which an increase in the number of microvessels and obvious proliferation of keratinized epithelial cells in wound margin were observed at each time point. (3) The content and the protein expression level of GM-CSF peaked on PID 3 in two groups, and they were (720.9 ± 0.9) pg/mL, 2.45 ± 0.10 in control group and (910.5 ± 1.3) pg/mL, 2.80 ± 0.48 in treatment group. The content of GM-CSF in treatment group was significantly higher than that in control group at each time point (with t values from 105.743 to 298.971, P values all equal to 0.000). The protein expression level of GM-CSF in treatment group was significantly higher than that in control group on PID 1, 5, and 7 (with t values from 4.070 to 5.275, P values all below 0.01). (4) The expression level of CD31 in treatment group was obviously higher than that in control group on PID 1, 3, and 7 (with t values from 7.237 to 26.401, P values all below 0.01). (5) The expression levels of mTOR and p-mTOR in treatment group were significantly higher than those in control group at each time point (with t values from 2.921 to 23.143, P < 0.05 or P < 0.01). In treatment group, the expression level of P70S6K was obviously higher than that in control group on PID 3, 5, and 7 (with t values from 2.950 to 5.275, P < 0.05 or P < 0.01), and the expression level of p-P70S6K was significantly higher than that in control group on PID 1, 3, and 7 (with t values from 3.307 to 22.793, P < 0.05 or P < 0.01). In treatment group, the expression level of 4E-BP1 was significantly lower than that in control group on PID 1, 3, and 5 (with t values from 2.449 to 6.431, P < 0.05 or P < 0.01), but the expression level of p-4E-BP1 was significantly higher than that in control group on PID 1, 3, and 7 (with t values from 5.522 to 11.613, P values all below 0.01).

CONCLUSIONSGM-CSF can promote wound healing in rats by activating mTOR signaling pathway through phosphorylating mTOR proteins and its downstream signal molecules P70S6K and 4E-BP1.

Animals ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; Wound Healing ; drug effects

This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy γ-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.
Animals ; Cell Cycle ; drug effects ; radiation effects ; Female ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; pharmacology ; Thymocytes ; drug effects ; radiation effects

This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.
Animals ; Dogs ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic System ; drug effects ; radiation effects ; Neutron Diffraction ; Recombinant Proteins ; administration & dosage ; pharmacology ; Survival Rate