Cefepime/amikacin in the empirical antibacterial therapy for patients with hemoblastosis of different forms]

The results of the use of cefepime (Maxipime) combination with amikacin vs ceftriaxon combination with amikacin in the treatment of 80 patients with different forms of hemoblastosis are presented. Severe infectious complications in the patients were associated with prolonged and deep neutropenia during inductive or antirelapsing chemotherapy. All the patients in the trial were from the group of high risk of infectious complications with the blood neutrophil count under 100 cells/microliter. The duration of neutropenia averaged 12 days (7 to 15). The average period of the treatment with cefepime and amikacin equaled to 13 days (8 to 16). The treatment with cefepime + amikacin was successful in 38 out of 40 patients (95%). The average period of the treatment with ceftriaxon and amikacin equaled to 14 days (7 to 18). The efficacy of the treatment with ceftriaxon + amikacin was 60% (24 patients out of 40).     

The role of cefepime, a 4th-generation cephalosporin, in treating patients with surgical sepsis]

Cefepime (Maxipime) was used in the management of 22 patients at the age of 18 to 73 years with the surgical sepsis syndrome (SAPS > 15). In 16 patients surgical sepsis was due to pancreatitis, appendititis, abdominal wound or trauma or complications after planned surgical interventions on the organs of the abdominal cavity. In the other 6 patients surgical sepsis was due to inflammatory processes in soft tissues after minor trauma. In 10 patients (group 1) cefepime was used after the pathogen verification and antibioticogram examination. In 12 patients (group 2) the antibiotic was used in the empirical therapy as the first line drug after the patients acceptance from another unit when the pathogen nature was obscure. Cefepime was administered intravenously in a dose of 2.0 g twice daily for 7 to 10 days in combination with metronidazole in a dose of 0.5 g thrice daily. After 5-6 days of the treatment the patients of group 1 were switched to the cefepime intramuscular regimen. The lethality totaled 18 per cent (4 patients). Three of them were from group 2. The patients died of progressive polyorgan insufficiency. It is characteristic that in no cases cefepime induced septic shock due to the endotoxin escape. No septicopyemia was as well observed even in the patients with verified bacteremia due to Staphylococcus aureus.     

3-Year experience of use of cefepime (Maxipime) for the treatment of hospital infections in a specialized surgical hospital]

Microbiological and clinical monitoring for 3 years (from 2001 to 2003) confirmed high clinical and microbiological efficacy of cefepime (Maxipime, Bristol-Myers-Squibb) in the treatment of infectious complications in patients with solid tumors in an oncologic hospital. It should be noted, however, that high efficacy of cefepime and wide ranges of the indications to its use do not allow to consider it as an agent for the treatment of all possible complications in such patients. The drug is not active against enterococci, not always clinically sufficiently effective in the treatment of Pseudomonas aeruginosa infections, it is impossible to use cefepime in monotherapy of suspected anaerobic infections. Therefore, widespread uncontrolled use of cefepime should be prohibited. It should be prescribed strictly by the indications with the account of the pathogen susceptibility, the infection severity and the recommended doses and regimens. The use of cefepime is undoubtedly valid when other antimicrobials fail or when empirical antimicrobial therapy of severe cases is required, including those under intensive care.     

Production of hydrolases by lactic acid bacteria and bifidobacteria and their antibiotic resistance

It was demonstrated that bifidobacteria and lactic acid bacteria B. adolescentis and Lactobacillus sp. synthesized extracellular enzymes cleaving glycoside bonds in the molecules of dextran, pectic acid, and soluble starch. The maximal production of extracellular beta-galactosidase by B. adolescentis 91-BIM and 94-BIM at a rate of 0.08 and 0.03 U/mg h was observed during the exponential growth phase at 5 and 12 h of cultivation, respectively. The cultures of bifidobacteria retained 60-70% of beta-galactosidase and alpha-amylase activities after six months of storage. The bifidobacterium strains studied were resistant to amphotericin and aminoglycosides (gentamicin, kanamycin, and netromycin). The lactam antibiotics (ampicillin, benzylpenicillin, bicillin 3, bicillin 5, and carbenicillin), the preparations inhibiting protein synthesis at the level of ribosomes (lincomycin), RNA polymerase inhibitors (rifampin), cephalosporin, and Maxipime inhibited the growth of bifidobacteria. Rifampin, erythromycin, amphotericin, Maxipime, Fortum, doxycycline, levomycetin, streptomycin, and the aminoglycosides netromycin, gentamicin, and kanamycin did not have an effect on the growth of Lactobacillus sp., whereas semisynthetic derivatives of penicillin, carbenicillin and ampicillin, inhibited its growth as well as Oxamp and lincomycin. The lactam antibiotics benzylpenicillin, bicillin 3, and bicillin 5 inhibited the growth of lactic acid bacilli by 30-90%.     

DMSO及RA对GPI-80分子表达的不同影响

以往的研究表明GPI-80的表达可能与髓系细胞的分化相关。DMSO及RA是两种不同的中性粒细胞的诱导分化剂,均可刺激HL-60白血病细胞向中性粒细胞分化。GPI-80是人糖基化磷脂酰肌醇锚糖蛋白,被认为是潜在的β2-黏合素分子依赖的白细胞黏附的调节剂,主要在人中性粒细胞上表达。本研究通过RT—PCR、流式细胞仪及Western—blot分析,检测分化细胞的GPI-80表达,并分析GPI-80的表达与CD11b及CD71表达之间的关系。结果表明GPI-80在RA诱导的类中性粒细胞上只有mRNA水平上的微弱表达,用流式细胞仪和Western—blot分析均检测不到,且RA可抑制GPI-80的表达;相反GPI-80在DMSO诱导的类中性粒细胞上有明显的表达,且随DMSO的浓度增加及诱导时间的延长而增强。GPI-80的表达出现在CD11b上调表达及CD71下调表达之后,提示GPI-80表达与DMSO诱导分化的类中性粒细胞的成熟密切相关。RA不能明确诱导GPI-80的表达,反而抑制GPI-80的表达,提示可能两者诱导HL-60细胞分化时所激活的信号传递通路不同。     

Production of hydrolases by lactic acid bacteria and bifidobacteria and their antibiotic resistance

It was demonstrated that bifidobacteria and lactic acid bacteria B. adolescentis and Lactobacillus sp. synthesized extracellular enzymes cleaving glycoside bonds in the molecules of dextran, pectic acid, and soluble starch. The maximal production of extracellular β-galactosidase by B. adolescentis 91-BIM and 94-BIM at a rate of 0.08 and 0.03 U/mg per h was observed during the exponential growth phase at 5 and 12 h of cultivation, respectively. The cultures of bifidobacteria retained 60–70% of β-galactosidase and α-amylase activities after six months of storage. The bifidobacterium strains studied were resistant to amphotericin and aminoglycosides (gentamicin, kanamycin, and netromycin). The lactam antibiotics (ampicillin, benzylpenicillin, bicillin 3, bicillin 5, and carbenicillin), the preparations inhibiting protein synthesis at the level of ribosomes (lincomycin), RNA polymerase inhibitors (rifampin), cephalosporin, and Maxipime inhibited the growth of bifidobacteria. Rifampin, erythromycin, amphotericin, Maxipime, Fortum, doxycycline, levomycetin, streptomycin, and the aminoglycosides netromycin, gentamicin, and kanamycin did not have an effect on the growth of Lactobacillus sp., whereas semisynthetic derivatives of penicillin, carbenicillin and ampicillin, inhibited its growth as well as Oxamp and lincomycin. The lactam antibiotics benzylpenicillin, bicillin 3, and bicillin 5 inhibited the growth of lactic acid bacilli by 30–90%.     

Acido‐ and neutrophilic temperate forest plants display distinct shifts in ecological pH niche across north‐western Europe

Ecological niches of organisms vary across geographical space, but niche shift patterns between regions and the underlying mechanisms remain largely unexplored. We studied shifts in the pH niche of 42 temperate forest plant species across a latitudinal gradient from northern France to boreo‐nemoral Sweden. We asked 1) whether species restrict their niches with increasing latitude as they reach their northern range margin (environmental constraints); 2) whether species expand their niches with increasing latitude as regional plant species richness decreases (competitive release); and 3) whether species shift their niche position toward more acidic sites with increasing latitude as the relative proportion of acidic soils increases (local adaptation). Based on 1458 vegetation plots and corresponding soil pH values, we modelled species response curves using Huisman–Olff–Fresco models. Four niche measures (width, position, left and right border) were compared among regions by randomization tests. We found that with increasing latitude, neutrophilic species tended to retreat from acidic sites, indicating that these species retreat to more favorable sites when approaching their range margin. Alternatively, these species might benefit from enhanced nitrogen deposition on formerly nutrient‐poor, acidic sites in southern regions or lag behind in post‐glacial recolonization of potential habitats in northern regions. Most acidophilic species extended their niche toward more base‐rich sites with increasing latitude, indicating competitive release from neutrophilic species. Alternatively, acidophilic species might benefit from optimal climatic conditions in the north where some have their core distribution area. Shifts in the niche position suggested that local adaptation is of minor importance. We conclude that shifts in the pH niche of temperate forest plants are the rule, but the directions of the niche shifts and possible explanations vary. Our study demonstrates that differentiating between acidophilic and neutrophilic species is crucial to identify general patterns and underlying mechanisms.     

Evidence of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> in human clinical samples in southwestern Slovakia over a 10-year period (2001–2010)

In the past, Pneumocystis jiroveci (formerly P. carinii) belonged to the Protozoa group, but the studies on structure of the cell wall and nucleotide sequence resulted in the reclassification of this organism in the kingdom Fungi. P. jiroveci is an opportunistic pathogen, responsible for pneumocystis pneumonia with frequent complications of immunocompromised patients. Delayed initiation of appropriate therapy increases the risk of death in immunocompromised patient. The aim of this work was to determine the prevalence of P. jiroveci from patients suspected of having respiratory tract infections in southwestern Slovakia over a 10-year period. Due to the increasing number of immunosuppressed persons, the diagnostic of P. jiroveci in patients with pulmonary complications is essential to improve recovery onsets. Effective diagnosis is currently based on microscopic examination and detection of parasite DNA by polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) and induced sputum. In total, 386 clinical samples originated from patients suspected of pneumocystis infection were tested within ten years. Requirements for diagnosis of the pathogen were growing during the period. Three hundred and sixteen BALs, 59 induced sputa, 10 lung biopsies and 1 liquor were subjected to the detection of P. jiroveci. P. jiroveci DNA was detected in 30 patients using PCR, but cysts of microorganism were present only in 4 cases by microscopy. The pathogen was confirmed in 24 BALs and 6 sputa samples. The presence of P. jiroveci has been demonstrated mainly in immunocompromised individuals with cancer (20), but also in patients with pneumonia (6+1 HIV), with unspecified parasitic diseases (1+1HIV) and with systemic lupus erythematosus (1).     

Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease

A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12-15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses.     

The cytochemical demonstration of cyanide resistant peroxidase does not identify eosinophils selectively

Potassium cyanide (KCN) resistant peroxidase is generally accepted by hematologists as a selective stain for the eosinophilic cell line. However, it has been demonstrated biochemically that not only the peroxidases of neutrophils but also those of eosinophils can be inhibited by KCN. Therefore, bone marrow smears of hematologically normal patients were subjected to the peroxidase reaction in the presence of varying concentrations of KCN. It was found that with increasing concentrations of KCN not only neutrophils but also eosinophils were inhibited. Moreover, there were always neutrophilic promyelocytes that were still positive when a considerable number of the eosinophils was already inhibited. Therefore, it can be concluded from our results as well as from biochemical data that there is no concentration of KCN which demonstrates the total of the eosinophilic cell line selectively. The implications of these findings are discussed.     

Role of Toll-like receptor 4 in innate immune responses in a mouse model of acute otitis media

Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study characterized the role of Toll-like receptor 4 in the innate immune responses to acute otitis media induced by NTHi in mice. We used C3H/HeJ mice, which have nonfunctional Toll-like receptor 4, and normal wild-type C3H/HeN mice. NTHi were injected into the tympanic bulla, and middle ear effusions and tissues were collected. In C3H/HeN mice, the severity of acute otitis media decreased promptly with a significant reduction in bacterial recovery from middle ear effusions 48 h after injection. In contrast, all C3H/HeJ mice had otitis media at all time points examined, and increasing bacterial counts from middle ear effusions were detected in C3H/HeJ mice 72 h after injection. Expression of intracellular adhesion molecule-1 by the middle ear mucosa paralleled the number of polymorphonuclear cells in the middle ear in both strains. The findings of transmission electron microscopy revealed that phagocytosis and phagosome maturation of polymorphonuclear cells was impaired in C3H/HeJ mice. Our findings indicate that Toll-like receptor 4 plays a part in the early accumulation and functional promotion of polymorphonuclear cells in the middle ear for eradicating NTHi infection.     

The isolation and cultivation of rabbit bone marrow mononuclear phagocytes

Rabbit bone marrow cells were cultured in a liquid medium in the presence of high concentrations of serum but in the absence of other added exogenous stimulating substances. Conditions were established that allow the selective proliferation of the precursor cells of the mononuclear phagocytes and their differentiation into macrophages. These cells were identified both on the basis of their morphological appearance as well as on several other properties (presence of Fc receptors at their surface, rapid phagocytosis of latex or India ink, continuous secretion of lysozyme). Their proliferation is preceded by the rapid degeneration of all the other cell types, including the granulocytes that are no longer found after 4 days of culture. Macrophage precursors (monoblasts and promonocytes) proliferate and persist in suspension until the 8th–10th day of culture when they become adherent. Essentially pure populations of macrophages could be maintained in culture for at least 4 weeks.     

Effect of altered hormonal balance in the mother-fetus system on body weight, the adrenal glands, thymus gland and peripheral blood leukocyte composition in the offspring

Pregnant rats have been injected intramuscularly with hydrocortisone-acetate or desoxycorticosterone-acetate (DOCA) for the III or the II-III trimesters of pregnancy. In the last case the animals are given not only greater doses of the hormones, but during a longer period. By the end of the pregnancy the drug dose decreases. In mother-rats after hydrocortisone injections the adrenals mass increases; after DOCA the body mass increases, and that of the adrenals drops. In the offspring hydrocortisone produces decline of the thymus and adrenals mass, as well as neutrophilic leucocytosis, lympho-, eosino-++- and monocytopenia. Just the opposite, DOCA results in lympho- and monocytosis, in increasing morphofunctional activity of monocytes. Common effects in hormonal action is demonstrated as underdevelopment of the adrenals, in decreasing thymus mass, in development of neutrophilic leucocytosis and eosinopenia. With increasing doses and duration of prenatal injections of corticosteroids in rats the mass of the adrenals and thymus drops even greater, stimulating effect of the hormones on the neutrophilic granulocytopoiesis decreases.     

Microspectrophotometric Studies of Romanowsky Stained Blood Cells. IV. Maturation of Myeloid and Erythroid Cell Lines in Bone Marrow

A quantitative characterization has been made of azure B/eosin stained cells from bone marrow. Two cell lines were followed: the myeloid line (white cell blast, promyelocyte, neutrophilic myelocyte, neutrophilic metamyelocyte, neutrophilic hand, neutrophilic segmented) and the erythroid line (rubriblast, prorubricyte, rubricyte, metarubricyte, diffusely basophilic erythrocyte, erythrocyte). A consensus scheme was used to obtain the “true” classification of the cells. Cell types were characterized by three methods: absorbance spectra, dye binding, and chromaticities. Within both cell lines nuclear maturation is accompanied by an overall increase in peak absorbance with little shift in the position of the maximum. Generally, binding of azure B and eosin increases; azure B dimer/monomer ratios show a slight downward trend during maturation. Changes in chromaticities are to bluish purples of increasing saturation. Cytoplasmic changes accompanying maturation are much more striking than nuclear changes, and again the two cell lines show similarities. Generally, there is decreased binding of azure B during maturation. In the erythroid line, the Soret band of hemoglobin becomes increasingly prominent. Chromaticities change from bluish purples to purplish pinks, particularly in the erythroid line.     

Cytokine and chemokine responses in pediatric patients with severe pneumonia associated with pandemic A/H1N1/2009 influenza virus

Severe pneumonia and leukocytosis are characteristic, frequently observed, clinical findings in pediatric patients with pandemic A/H1N1/2009 influenza virus infection. The aim of this study was to elucidate the role of cytokines and chemokines in complicating pneumonia and leukocytosis in patients with pandemic A/H1N1/2009 influenza virus infection. Forty‐seven patients with pandemic A/H1N1/2009 influenza virus infection were enrolled in this study. Expression of interleukin (IL)‐10 (P = 0.027) and IL‐5 (P = 0.014) was significantly greater in patients with pneumonia than in those without pneumonia. Additionally, serum concentrations of interferon‐γ (P = 0.009), tumor necrosis factor‐α (P = 0.01), IL‐4 (P = 0.024), and IL‐2 (P = 0.012) were significantly lower in pneumonia patients with neutrophilic leukocytosis than in those without neutrophilic leukocytosis. Of the five serum chemokine concentrations assessed, only IL‐8 was significantly lower in pneumonia patients with neutrophilic leukocytosis than in those without leukocytosis (P = 0.001). These cytokines and chemokines may play important roles in the pathogenesis of childhood pneumonia associated with A/H1N1/2009 influenza virus infection.     

Hematopoiesis during remote period after acute radiation syndrome

Based on the long (19.7 +/- 1.8 year) hemopoiesis follow-up study in 152 patients after acute radiation syndrome (ARS) as a result of exposure to gamma-, gamma-beta and gamma-eta radiation in a wide dose range (1.2-9.8 Gy) it was detected that cytopenia appears in the late consequences period: thrombocytopenia was found in 26.9% cases, leukocytopenia, neutropenia and lymphocytopenia--in 13.1% patients. A higher ARS degree causes the increase of various disorders (cytopenia and cytosis) in the late period. It reflects a tight interrelation between blood cell contents and radiation dose. Frequency of cytopenias increases if such somatic disorders: persistent hepatitis, hepatic cirrhosis and late radiation ulcers as appear.     

Microspectrophotometric studies of Romanowsky stained blood cells. IV. Maturation of myeloid and erythroid cell lines in bone marrow

A quantitative characterization has been made of azure B/eosin stained cells from bone marrow. Two cell lines were followed: the myeloid line (white cell blast, promyelocyte, neutrophilic myelocyte, neutrophilic metamyelocyte, neutrophilic band, neutrophilic segmented) and the erythroid line (rubriblast, prorubricyte, rubricyte, metarubricyte, diffusely basophilic erythrocyte, erythrocyte). A consensus scheme was used to obtain the "true" classification of the cells. Cell types were characterized by three methods: absorbance spectra, dye binding, and chromaticities. Within both cell lines nuclear maturation is accompanied by an overall increase in peak absorbance with little shift in the position of the maximum. Generally, binding of azure B and eosin increases; azure B dimer/monomer ratios show a slight downward trend during maturation. Changes in chromaticities are to bluish purples of increasing saturation. Cytoplasmic changes accompanying maturation are much more striking than nuclear changes, and again the two cell lines show similarities. Generally, there is decreased binding of azure B during maturation. In the erythroid line, the Soret band of hemoglobin becomes increasingly prominent. Chromaticities change from bluish purples to purplish pinks, particularly in the erythroid line.     

Inhaled corticosteroid effects both eosinophilic and non-eosinophilic inflammation in asthmatic patients

AIM: To determine induced sputum cell counts and interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha) and leukotriene B4 (LTB4) levels as markers of neutrophilic inflammation in moderate persistent asthma, and to evaluate the response to inhaled steroid therapy. METHODS: Forty-five moderate asthmatic patients and 10 non-smoker controls were included in this study. All patients received inhaled corticosteroid (800 microg of budesonide) for 12 weeks. Before and after treatment pulmonary function tests were performed, and symptom scores were determined. Blood was drawn for analysis of serum inflammatory markers, and sputum was induced. RESULTS: Induced sputum cell counts and inflammatory markers were significantly higher in patients with asthma than in the control group. The induced sputum eosinophil counts of 12 patients (26%) were found to be less than 5%, the non-eosinophilic group, and sputum neutrophil counts, IL-8 and TNF-alpha levels were significantly higher than the eosinophilic group (neutrophil, 50+/-14% versus 19+/-10%, p<0.01). In both groups, there was a significant decrease in sputum total cell counts and serum and sputum IL-8, TNF-alpha and LTB4 levels after the treatment. There was no change in sputum neutrophil counts. Although the sputum eosinophil count decreased only in the eosinophilic subjects, there was no significant difference in inflammatory markers between the groups. The symptom scores were significantly improved after treatment, while the improvement did not reach statistical significance on pulmonary function test parameters. CONCLUSION: Notably, in chronic asthma there is a subgroup of patients whose predominant inflammatory cells are not eosinophils. Sputum neutrophil counts and neutrophilic inflammatory markers are significantly higher in these patients. In the non-eosinophilic group, inhaled steroid caused an important decrease in inflammatory markers; however, there was no change in the sputum eosinophil and neutrophil counts.     

Optimization of extracellular lipase production by Geotrichum sp. using factorial design

Response surface methodology was employed to study the effects of carbon source (soy oil, olive oil and glucose) and nitrogen source concentrations (corn steep liquor and NH(4)NO(3)) on the lipase production by Geotrichum sp. The experiment included a 2(4) central composite rotatable design (CCRD) and four others 2(3) CCRD. According to the responses from the experimental designs, the effects of each variable were calculated and the interactions between them were determined. The response surface methodology was applied for the optimization of the nutrient concentrations in the culture medium for the enzyme production, at 30 degrees C. The optimum medium composition for lipase production by Geotrichum sp. was ammonium nitrate 2.1-2.5%, corn steep liquor 13-15% and soy oil 0.6% as carbon source, which lead to a lipase activity of about 20 U/ml. Using olive oil as carbon source, the optimum composition was ammonium nitrate 0.8-1%, corn steep liquor 13-15% and olive oil 0.6%, leading to an activity of 17 U/ml.     

Thioredoxin-1 Protects against Neutrophilic Inflammation and Emphysema Progression in a Mouse Model of Chronic Obstructive Pulmonary Disease Exacerbation

Background

Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression. However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established. Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema. We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.

Results

Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity. Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice. Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice. Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression. Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS. Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated. Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.

Conclusion

Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression. Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation.