Hierarchical hollow superstructure cobalt selenide bird nests for high-performance lithium storage.

The inferior cycling performance caused by large volume variation is the main problem that restricts the application of cobalt selenides in lithium-ion batteries. Herein, we synthesize raspberry-like Co-ethylene glycol precursor. It is further selenized into the hierarchical hollow superstructure CoSe2/CoSe bird nests that are assembled by the hollow nanosphere units of CoSe2 and CoSe nanocrystalline. CoSe2/CoSe bird nests achieve excellent cycling performance, high reversible capacity and satisfactory rate capability (1361 mAh/g at 1 A/g after 1000 cycles, 579 mAh/g at 2 A/g after 2000 cycles, 315 mAh/g at 5 A/g after 1000 cycles). Electrochemical kinetics analyses and ex-situ material characterization reveal that the surface capacitive behavior controls the electrochemical reaction, and the composite has low reaction impedance, fast and stable Li+ diffusion, and superior structural stability. The superior lithium storage performance is attributed to the unique superstructure bird nest. Large specific surface area, abundant hierarchical pores and the opening mouth result in high electrochemical activity, which induces high reversible capacity. The small hollow nanosphere units, the sufficiently thick hierarchical porous superstructure shell and the large hollow interior bring about the strong synergistic effect to improve cycling performance. The intimately coupling of CoSe2/CoSe nanocrystalline and the hollow nanosphere units guarantees high conductivity. This work has greatly enriched the understanding of structure design of high-performance cobalt selenide anodes.

Intimately coupled Mn3O4nanocrystalline@3D honeycomb hierarchical porous network scaffold carbon for high-performance cathode of aqueous zinc-ion batteries.

Herein, 3D honeycomb hierarchical porous network scaffold carbon is synthesized by a unique PVP-SiO2-boiling method with the boiling bubbles as soft template and SiO2nanospheres as hard template. Then MnO2nanosheets intimately grow on the carbon matrix and are further decomposed to Mn3O4nanocrystalline with size of 7-9 nm. The obtained Mn3O4nanocrystalline@3D honeycomb hierarchical porous network scaffold carbon has abundant mesopores and large specific surface area (92 m2g-1). When used as a cathode material for zinc-ion batteries, the synthesized composites exhibit high reversible capacity (546.2 mAh g-1at 0.5 A g-1), remarkable cycling stability (discharge capacity of 97.8 mAh g-1at 3 A g-1after 600 cycles) and superior rate capability (15.7 mAh g-1at 10 A g-1). The kinetics analyses indicate zinc storage mechanism includes diffusion process and capacitive process of Zn2+and H+ions, and the capacitive storage is dominant. The outstanding zinc storage performance benefits from the structural advantages. The unique carbon matrix improves electronic conductivity of Mn3O4, facilitates penetration of electrolyte, and well supports Mn3O4nanocrystalline. The small size and large specific surface area of Mn3O4nanocrystalline induce significant capacitive storage effect.

Pomegranate-like C@TiO2 mesoporous honeycomb spheres for high performance lithium ion batteries.

Pomegranate-like C@TiO2 mesoporous honeycomb spheres have been synthesized through two simple steps: formation of TiO2 mesoporous honeycomb spheres and the coating of polypyrrole followed by carbonization. TiO2 mesoporous honeycomb spheres are of large specific surface area of 153 m2 g-1 and contain abundant mesopores, which leads to high electrochemical activity and good kinetic performance of TiO2. A layer of amorphous carbon shell with the thickness of 30-40 nm tightly encapsulates a TiO2 mesoporous honeycomb sphere, forming a novel pomegranate-like small sphere, which significantly improves electronic conductivity and structural stability of TiO2. Benefiting from the unique pomegranate-like structure, C@TiO2 mesoporous honeycomb spheres exhibit high specific capacity, stable long-term cycling performance and good rate capability as an anode material for lithium ion batteries (LIBs). After 500 cycles at 1 C, the discharge capacity still reaches 184 mAh g-1. The electrochemical performance is superior to pure TiO2 mesoporous honeycomb spheres and most of the reported high-performance TiO2-based composites. This work provides a new high-performance TiO2-carbon-based composite material for LIBs as well as a new valuable research strategy.

[Application of external diaphragm pacemaker combination with high-flow nasal cannula in offline patients with postoperative severe cerebral hemorrhage].

Objective: To investigate the offline clinical effect of external diaphragm pacemaker (EDP) combination with High-flow nasal cannula oxygen therapy in postoperative severe cerebral hemorrhage patients. Methods: A total of 123 severe postoperative severe cerebral hemorrhage patients with tracheotomy and mechanical ventilation (MV) were selected, who were admitted in NICU of PLA Rocket Force Characteristic Medical Center from October 2016 to December 2019. These patients were randomly divided into the High-flow nasal cannula (HFNC) group (n=63) and HFNC+EDP group (n=60). In the HFNC group, the HFNC was given to the patients who were off ventilator. The HFNC+EDP group was added on the basis of treatment in the HFNC group, once a day and 30 minutes each time. Results: Compared to the HFNC group, the oxygenation index (OI) of the HFNC+EDP group was higher in the next 1, 12, 24 and 48 hour [(209±15) mmHg vs (218±18) mmHg, (215±14) mmHg vs (222±17) mmHg, (223±13) mmHg vs (235±15) mmHg, (236±7) mmHg vs (257±12) mmHg,P<0.05]. The offline time was shorter [(13±3) d vs (12±3) d,P<0.05]. The excursion of diaphragm was higher [(1.94±0.08) cm vs (2.91±0.11) cm,P<0.05]. The length of stay in NICU was shorter [(33±14) d vs (28±9) d,P<0.05]. The Glasgow Coma Scale (GCS) was higher when being discharged from the NICU (5.9±2.1 vs 7.8±0.4, P<0.05) and the hospital (9.9±2.1 vs 11.0±2.0, P<0.05). Conclusions: EDP combination with HFNC can increase the excursion of diaphragm, shorten the offline time and length of stay in the NICU, thereby enhancing the early recovery and improving the prognosis.

Watermelon-like TiO2 nanoparticle (P25)@microporous amorphous carbon sphere with excellent rate capability and cycling performance for lithium-ion batteries.

To overcome the inferior rate capability and cycling performance of TiO2 nanomaterials as an anode material of lithium-ion batteries, we encapsulate TiO2 nanoparticles (P25) in carbon spheres through a facile pyrrole polymerization and carbonization. Material characterization demonstrates TiO2 nanoparticles are uniformly embedded in microporous amorphous carbon spheres, forming a watermelon-like structure. P25@C exhibits excellent high rate capability with average discharge capacity of 496, 416, 297, 240, 180, 99, 49 and 25 mAh g-1 at current rate of 0.5C, 1C, 5C, 10C, 20C, 50C, 100C and 200C, which shows superior long-term cycling performance with discharge capacity of 106.9 mAh g-1 at 20C after 5000 cycles. The capacity loss rate is only 0.008% per cycle. The outstanding lithium storage performance is ascribed to the watermelon-like composite structure, which remarkably improves electronic conductivity and structure stability of TiO2 nanoparticles. More importantly, the agglomeration of TiO2 nanoparticles is eliminated, and the entire surface of every TiO2 nanoparticle participates in the electrochemical reaction, which brings about an intense capacitive Li storage effect and leads to the high specific capacity and excellent rate capability of P25@C. This is confirmed through qualitative and quantitative analysis of the contributions from surface capacitive storage and bulk intercalation storage to the total capacity of the composite.

Construction of Co3O4 three-dimensional mesoporous framework structures from zeolitic imidazolate framework-67 with enhanced lithium storage properties.

High-porosity mesoporous framework structures are attractive for electrochemical energy storage and other applications. Herein we demonstrate a novel synthesis strategy to make zeolitic imidazolate framework-67 oxidize to a Co3O4 three-dimensional mesoporous framework structure. This strategy relies on the oxygen-limitation effect of the closed nanocage and the affinity effect of polyvinylpyrrolidone towards zeolitic imidazolate framework-67. Several TiO2 nanospheres, as the unique structure junctions, are uniformly embedded within the Co3O4 framework to enhance the framework strength. The TiO2/hydrous titania polyhedron nanocage, as the protecting shell, further encapsulates the Co3O4 framework, forming a perfect capsule-type hybrid. As anode materials for lithium-ion batteries, TiO2@Co3O4 framework capsules show superior lithium storage performance with high reversible capacity, stable cycling life and good rate capability. A reversible capacity of 1042 mAh g-1 can be delivered after 200 cycles at a current density of 300 mA g-1. The average discharge capacity over 200 cycles reaches 926 mAh g-1. This demonstrates the superiority of this material structure and its great potential as an anode for high-performance lithium-ion batteries. This work indicates a new strategy to take advantage of metal-organic frameworks to synthesize their mesoporous framework derivatives.

Electron transport and visible light absorption in a plasmonic photocatalyst based on strontium niobate.

Semiconductor compounds are widely used for photocatalytic hydrogen production applications, where photogenerated electron-hole pairs are exploited to induce catalysis. Recently, powders of a metallic oxide (Sr1-xNbO3, 0.03

Efficacy of a quadruple therapy regimen for Helicobacter pylori eradication after partial gastrectomy.

We aimed to evaluate the effectiveness and safety of bismuth-containing quadruple therapy plus postural change after dosing for Helicobacter pylori eradication in gastrectomized patients. We compared 76 gastric stump patients with H. pylori infection (GS group) with 50 non-gastrectomized H. pylori-positive patients who met the treatment indication (controls). The GS group was divided into GS group 1 and GS group 2. All groups were administered bismuth potassium citrate (220 mg), esomeprazole (20 mg), amoxicillin (1.0 g), and furazolidone (100 mg) twice daily for 14 days. GS group 1 maintained a left lateral horizontal position for 30 min after dosing. H. pylori was detected using rapid urease testing and histologic examination of gastric mucosa before and 3 months after therapy. Mucosal histologic manifestations were evaluated using visual analog scales of the updated Sydney System. GS group 1 had a higher prevalence of eradication than the GS group 2 (intention-to-treat [ITT]: P=0.025; per-protocol [PP]: P=0.030), and the control group had a similar prevalence. GS group 2 had a lower prevalence of eradication than controls (ITT: P=0.006; PP: P=0.626). Scores for chronic inflammation and activity declined significantly (P<0.001) 3 months after treatment, whereas those for atrophy and intestinal metaplasia showed no significant change. Prevalence of adverse reactions was similar among groups during therapy (P=0.939). A bismuth-containing quadruple therapy regimen plus postural change after dosing appears to be a relatively safe, effective, economical, and practical method for H. pylori eradication in gastrectomized patients.

Efficacy of a quadruple therapy regimen for Helicobacter pylori eradication after partial gastrectomy

We aimed to evaluate the effectiveness and safety of bismuth-containing quadruple therapy plus postural change after dosing for Helicobacter pylori eradication in gastrectomized patients. We compared 76 gastric stump patients with H. pylori infection (GS group) with 50 non-gastrectomized H. pylori-positive patients who met the treatment indication (controls). The GS group was divided into GS group 1 and GS group 2. All groups were administered bismuth potassium citrate (220 mg), esomeprazole (20 mg), amoxicillin (1.0 g), and furazolidone (100 mg) twice daily for 14 days. GS group 1 maintained a left lateral horizontal position for 30 min after dosing. H. pylori was detected using rapid urease testing and histologic examination of gastric mucosa before and 3 months after therapy. Mucosal histologic manifestations were evaluated using visual analog scales of the updated Sydney System. GS group 1 had a higher prevalence of eradication than the GS group 2 (intention-to-treat [ITT]: P=0.025; per-protocol [PP]: P=0.030), and the control group had a similar prevalence. GS group 2 had a lower prevalence of eradication than controls (ITT: P=0.006; PP: P=0.626). Scores for chronic inflammation and activity declined significantly (P<0.001) 3 months after treatment, whereas those for atrophy and intestinal metaplasia showed no significant change. Prevalence of adverse reactions was similar among groups during therapy (P=0.939). A bismuth-containing quadruple therapy regimen plus postural change after dosing appears to be a relatively safe, effective, economical, and practical method for H. pylori eradication in gastrectomized patients.

Stem cell factor in combination with granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF synergistically increases granulopoiesis in vivo.

Recombinant rat stem cell factor (rrSCF) and recombinant human granulocyte colony-stimulating factor (G-CSF) coinjected for 1 week in rats cause a synergistic increase in mature marrow neutrophils accompanied by a striking decrease in erythroid and lymphoid marrow elements. The spleens of the same rats show increased granulopoiesis as well as increased erythropoiesis as compared with the spleens of rats treated with either growth factor alone. Splenic extramedullary erythropoiesis may act to compensate for the decrease in marrow erythropoiesis. The coinjection of rrSCF and G-CSF causes an increase in marrow mast cells at the end of 1 week, but the increase is much less than in rrSCF-alone-treated rats. The combination of rrSCF and G-CSF increases the rate of release of marrow neutrophils into the circulation and causes a dramatic synergistic peripheral neutrophilia, beginning especially after 4 days of treatment. Colony-forming assays of all experimental groups showed a synergistic increase in colony-forming unit granulocyte-macrophage (CFU-GM) in the marrow, but not in peripheral blood, after coincubation with SCF plus granulocyte-macrophage CSF (GM-CSF) as opposed to GM-CSF alone, showing anatomic compartmentalization between a more primitive marrow CFU-GM subset and a more mature peripheral blood CFU-GM subset. In vivo daily administration of SCF plus GM-CSF results in a synergistic increase in marrow neutrophils, but not the striking synergistic increase in circulating neutrophils that is observed with SCF plus G-CSF.

The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate.

Endotoxin (LPS), one of the major proinflammatory constituents of the cell walls of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1) and tumor necrosis factor (TNF) messenger RNA (mRNA), peaking at 1 hour in vitro. Intratracheal injection of LPS induces IL-1 and TNF mRNA expression in vivo in whole-lung RNA preparations. Interleukin-1 mRNA is not constitutively detected. In the case of TNF, however, a constitutively-expressed hybridization band is noted at 1.6 kb, whereas the LPS-induced hybridization band is noted at approximately 1.95 kb. Intratracheal injection of LPS induces an intra-alveolar inflammatory reaction composed of a neutrophilic exudate, peaking at 6 to 12 hours, a monocytic exudate peaking at 24 hours, and a lymphocytic exudate peaking at 48 hours, as quantitated by bronchoalveolar lavage. Intratracheal injection of IL-1 recapitulates the kinetics and relative magnitudes of the acute neutrophilic and chronic monocytic and lymphocytic inflammatory sequence. Intratracheal injection of TNF also induces an acute intraalveolar neutrophilic exudate, but TNF is much less potent of an inflammatory stimulus than IL-1. The effects of recombinant IL-1 and TNF are not due to LPS contamination, as shown by abrogation of the cytokines' inflammatory activity by boiling. In conclusion, LPS induces IL-1 and TNF mRNA expression in vitro in alveolar macrophages and in vivo in pulmonary tissue, and intratracheal injection of IL-1 and TNF recapitulates the LPS-induced pulmonary inflammatory sequence, strongly supporting the hypothesis that these cytokines play an important in vivo role in the pathogenesis of gram-negative bacterial pneumonia.

Endotoxin-induced cytokine gene expression in vivo. III. IL-6 mRNA and serum protein expression and the in vivo hematologic effects of IL-6.

Endotoxin (LPS) at sublethal doses injected i.v. into rats was found to induce IL-6 mRNA expression peaking at 1 to 2 h in whole organ RNA preparations of the spleen, liver, lung, bowel, and kidney. IL-6 serum protein levels also peaked at 2 h. TNF and IL-1, generally considered to be among the most rapidly released cytokines, also induced IL-6 expression. IL-6 in turn inhibited TNF and IL-1 expression, suggesting that IL-6 may be part of a negative feedback mechanism in the cytokine cascade. Dexamethasone down-regulated and Corynebacterium parvum up-regulated IL-6 expression, although the possibility cannot be excluded that these immunomodulating factors may in part have exerted their effects indirectly via the up- and down-regulation of TNF and IL-1. IL-6 injected i.v. at a pathophysiologically relevant dose caused a peripheral neutrophilia and mild myeloproliferative effect in the bone marrow.

The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation.

Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1). Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation. In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra). The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage. The LPS-induced emigration of neutrophils was inhibited by as much as 45%. Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta. Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone. Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation. In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.

The erythropoietic effects of interleukin 6 and erythropoietin in vivo.

The purpose of this investigation was to compare the erythropoietic effects of recombinant interleukin 6 (IL-6) and recombinant erythropoietin (EPO) on the marrow and peripheral blood in vivo. IL-6 administered to rats as a single i.v. injection induces a selective erythroid hyperplasia of the marrow's late normoblasts at 12 and 24 h with a return to preinjection numbers of normoblasts at 48 and 72 h. The hyperplasia of late normoblasts in the marrow is accompanied by a left-shifted peripheral reticulocytosis. Daily injection of IL-6 does not induce any effects on the erythroid population of the marrow or circulation beyond those of a single injection. After daily administration of IL-6 for 4 or 7 days, the erythroid differential in the marrow and the peripheral reticulocyte count are equal to negative control values, indicating a rapid tachyphylaxis to the erythropoietic effect of IL-6. In contrast to IL-6, EPO administered as a single i.v. injection induces a panerythroid marrow hyperplasia with sequential peak increases in pronormoblasts and early normoblasts at 24 h, intermediate normoblasts at 24-48 h, and late normoblasts at 72 h. The peripheral reticulocyte count mirrors the development of erythroid precursors in the marrow by demonstrating an increasing left-shifted reticulocytosis between 24 and 72 h. Daily injection of EPO for 7 days induces a striking erythroid hyperplasia and a myeloid hypoplasia in the marrow. In summary, IL-6 in vivo is a differentiation factor that rapidly induces tolerance to its own effect, whereas EPO in vivo affects all stages of erythropoiesis and sustains erythropoiesis indefinitely. IL-6 may be one of the non-EPO factors in pokeweed mitogen spleen cell-conditioned medium that has been reported by previous investigators to enhance erythropoiesis, although many of those factors were thought to act upon an earlier stage of erythropoiesis. IL-6 is unlikely to exert an indirect erythropoietic effect in vivo via the induction of EPO because the sera of IL-6-treated rats did not contain elevated levels of EPO and because the effects of exogenously administered IL-6 and EPO are so different.

Hematologic effects of recombinant murine granulocyte-macrophage colony-stimulating factor on the peripheral blood and bone marrow.

Recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was noted to support rat bone marrow colony formation in vitro. The in vivo hematologic effects of a single intravenous injection of murine GM-CSF were therefore investigated. Doses of murine GM-CSF between 0.1 and 5 micrograms/rat caused an increasing leukocytosis that did not further increase with a dose of 25 micrograms/rat. In contrast, human GM-CSF at 25 micrograms/rat did not induce any significant peripheral hematologic effects. Murine GM-CSF induced peripheral neutrophilia and monocytosis, peaking between 4 and 8 hours and subsiding to baseline by 12 hours. Neutropenia and monocytopenia, which reached a nadir at 15 minutes, preceded the leukocytosis, suggesting that GM-CSF activates these leukocytes and causes transient intravascular margination. A mild lymphopenia occurred between 2 to 8 hours. The bone marrow at 6 hours after injection of GM-CSF demonstrated a variable and slight left-shifted myeloid hyperplasia most noticeable at the level of promyelocytes and myelocytes, suggesting a myeloproliferative effect. The marrow at 6 hours also demonstrated a decrease in mature neutrophils, documenting that the marrow contributes to the increased number of circulating neutrophils. Once-daily injection of GM-CSF for 7 days induced a repetitive daily neutrophilia of the same magnitude. The marrow after 1 week of injections did not show a generalized myeloid hyperplasia, but did show an increase in eosinophils and a decrease in lymphocytes. Granulocyte-macrophage colony-stimulating factor plus granulocyte colony-stimulating factor (G-CSF) have been reported to synergize in vitro in both mouse and human bone marrow colony assays. However GM-CSF plus G-CSF in vivo, administered as either a single injection or as daily injections for 1 week, were found in the present study to induce, at most, an additive effect on circulating numbers of neutrophils. It is concluded that murine GM-CSF will be useful in the rat model to study the in vivo hematoreconstitutive effects of GM-CSF alone and in combination with other hematologic growth factors. The relatively rapid kinetics and lesser magnitude of GM-CSF-induced neutrophilia and monocytosis, as compared to G-CSF and M-CSF, respectively, and the lesser myeloproliferative effect of GM-CSF in bone marrow smears, as compared to G-CSF, might be taken to suggest that GM-CSF's natural activity is predominantly as an inflammatory rather than a myeloproliferative factor.

In vivo hematologic effects of recombinant human macrophage colony-stimulating factor.

Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF-induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.

Acute and subacute hematologic effects of multi-colony stimulating factor in combination with granulocyte colony-stimulating factor in vivo.

Multi-colony stimulating factor (Multi-CSF, interleukin-3, IL-3) and granulocyte-CSF (G-CSF) administered concurrently as an intravenous (IV) injection induce a peripheral neutrophilia that is approximately additive in comparison with the neutrophilia induced by IL-3 and G-CSF individually. The bone marrow (BM) at 12 hours is depleted of mature neutrophils and shows a left-shifted myeloid hyperplasia, consistent with the neutrophil-releasing and myeloproliferative activities of both IL-3 and G-CSF individually. The BM at 24 hours shows a replenished reserve of mature neutrophils and a synergistic left-shifted myeloid hyperplasia as compared with IL-3 and G-CSF alone. Daily IV injections of IL-3 plus G-CSF for 1 week also induce an approximately additive daily peripheral neutrophilia. The BM after a week's administration of IL-3 plus G-CSF shows a generalized myeloid hyperplasia with a synergistic increase in mature neutrophils as compared with IL-3 or G-CSF alone. Daily injection of IL-3 plus G-CSF induced a significant decrease in erythroid, lymphoid, and eosinophilic marrow precursors, possibly owing to a myelophthisic effect of the myeloid hyperplasia and despite the fact that IL-3 alone induced a significant erythroid hyperplasia.

Acute in vivo effects of IL-3 alone and in combination with IL-6 on the blood cells of the circulation and bone marrow.

Recombinant human IL-3 administered intravenously to rats as a single injection induced peripheral neutrophilia and monocytosis beginning at 4 to 6 hours after injection, peaking at 8 hours, and subsiding to normal by 12 to 24 hours. IL-3 did not induce an initial neutropenia such as accompanies endotoxin-, G-CSF-, and TNF-induced neutrophilia, or lymphopenia such as accompanies endotoxin-, IL-1-, and TNF-induced neutrophilia. The IL-3-induced peripheral neutrophilia was accompanied by a decrease in mature marrow neutrophils, indicating that the mechanism of neutrophilia was through marrow release rather than by demargination, which occurs after the administration of epinephrine or IL-6. The release of mature marrow neutrophils further suggests that IL-3 either has intrinsic neutrophil releasing activity or indirectly causes neutrophil release through the gene expression of a second cytokine. IL-3 induced a striking left-shifted myeloid hyperplasia in the bone marrow at 8 hours that morphologically was very similar to that observed after administration of endotoxin, a finding consistent with the hypothesis of previous investigators that endotoxin may in part act indirectly on hematopoietic cells by eliciting local marrow production of IL-3. Finally, IL-3 induced an increase in marrow pronormoblasts at 8 hours, consistent with the in vitro proliferative effect of IL-3 on erythroid stem cells. The combination of IL-3 and IL-6 induced a synergistic peripheral neutrophilia and monocytosis and a striking synergistic increase in marrow mast cells. The combination of IL-3 and IL-6 also induced an erythroid and left-shifted myeloid hyperplasia such as would be expected given the individual effects of these hematopoietic growth factors.