Bacterial Colonization Of Lungs Research Articles

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

Objective: The median length of survival for cystic fibrosis (CF) has significantly increased in recent years; however, this means that endocrine complications are more frequently observed in affected patients. This research was aimed at evaluating the frequency, clinical and paraclinical features, and the treatment of linear growth and pubertal disturbances, vitamin D insufficiency/deficiency, CF-related bone disease, and adrenal and thyroid function disturbances in patients with CF, as well as to explore their association with lung function and colonization. Method: A cross-sectional study with a retrospective collection of information from patients under 18 years of age with a confirmed diagnosis of CF, evaluated on an outpatient or in-hospital basis by a pediatric pulmonologist or endocrinologist, or in a multidisciplinary CF consultation, between January 2011–December 2020. Results: A total of 87 patients were included. A high frequency of endocrinopathies was found. Vitamin D insufficiency/deficiency was persistent despite cholecalciferol supplementation in 72%, short stature in 38%, pubertal delay in 26%, and thyroid axis disorders in 8% of cases. Bone disease involving densitometry and adrenal insufficiency secondary to chronic corticosteroid use were also frequent among the screened subjects (44% [n=16] and 12% [n=51], respectively). No significant differences were found for pulmonary function or bacterial lung colonization in the context of any endocrinopathies. Conclusion: Endocrine comorbidities are frequent in patients with CF, and early recognition improves the prognosis and quality of life in these patients. The findings for this cohort ratify the importance of multidisciplinary management of patients with CF.

620 Evolution of bacterial lung colonization status after 1 year of treatment with elexacaftor-tezacaftor-ivacaftor in 198 French adults with cystic fibrosis

620 Evolution of bacterial lung colonization status after 1 year of treatment with elexacaftor-tezacaftor-ivacaftor in 198 French adults with cystic fibrosis

The Levels of the Human-β-Defensin-2 and LL-37 in the Sputum of Children with Cystic Fibrosis: A Case–control Study and Literature Review

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder with an autosomal-recessive type of inheritance. Based on their host-defending and pro-inflammatory functions, antimicrobial peptides (AMPs) likely have one of the central roles in the pathogenesis of lung disease in CF. AIM: The purpose of the study was to measure the concentration of AMPs in the sputum of children with CF and evaluate any correlation with a bacterial profile of the lungs. METHODS: Lung colonization was evaluated using a culture-dependent method, sputum was utilized. A sandwich-ELISA was used to measure hBD-2 and hCAP-18/LL-37 in the sputum. RESULTS: There were 27 children enrolled in the study group, median age of inclusion was 11.4 (8.5; 14.8) years old. The control group consisted of 14 children, 11.6 (8.6; 12.6) years old. The concentration of AMPs was not correlating with participants` age (rs = −0.286, p = 0.148 – defensin hDB-2; rs = −0.084, p = 0.676 – cathelicidin hCAP-18/LL-37). The concentration of hBD-2 was from 64.01 to 813.61 pg/mL. The concentration of hCAP-18/LL-37 was from 3.24 to 35.98 ng/mL. There were significant differences in the content of AMPs on respiratory samples between study and control group (U = 976.5, p = 0.001 – for hBD-2; U = 1080.5, p < 0.001). The correlation between current infection Pseudomonas aeruginosa and concentration of hBD-2 (rs = 0.167; p = 0.406) was not found. However, the presence of P. aeruginosa correlated with density of neutrophilic infiltration (rs = 0.622; p = 0.001). The concentration of hBD-2 showed direct medium correlation with total cells count (rs = 0.881, p < 0.001). Correlation between current infection P. aeruginosa and concentration of hCAP-18/LL-37 (rs = 0.788; p < 0.001) was observed. With increases in total cell count and relative neutrophils count, the concentration of hCAP-18/LL-37 was increased and the power of the association was medium (rs = 0.453; p = 0,018; rs = 0,592; p = 0,001). The correlation between concentrations of hBD-2 and hCAP-18/LL-37 (rs = 0.316, p > 0.1) was not found. CONCLUSIONS: Measured AMPs correlated with cellular inflammatory markers and, probably, their overexpression is dedicated to stimulating a cellular component of innate immune response; there was no correlation between bacterial colonization of lungs and levels of hBD-2, so our findings sustain that P. aeruginosa is a leading but non-single contributor to persistent local inflammation in polymicrobial lungs.

RELATION BETWEEN BACTERIAL COLONIZATION IN LUNGS AND LEVELS OF 25-HYDROXYVITAMIN D AND ANTIMICROBIAL PEPTIDE LL-37 IN CHILDREN WITH CYSTIC FIBROSIS

The aim of the study was to assess the bacterial colonization in lungs of children with cystic fibrosis based on the antimicrobial peptide cathelicidin and 25-hydroxycholecalciferol in the serum. Study showed significant correlation between P. aeruginosa infection and cathelicidin and 25-hydroxycholecalciferol levels.

Antimicrobial Coating Prevents Ventilator-Associated Pneumonia in a 72 hour Large Animal Model

BackgroundThe primary goal of this study was to demonstrate that endotracheal tubes coated with antimicrobial lipids plus mucolytic or antimicrobial lipids with antibiotics plus mucolytic would significantly reduce pneumonia in the lungs of pigs after 72 hours of continuous mechanical ventilation compared to uncoated controls. Materials and MethodsEighteen female pigs were mechanically ventilated for up to 72 hours through uncoated endotracheal tubes, endotracheal tubes coated with the antimicrobial lipid, octadecylamine, and the mucolytic, N-acetylcysteine, or tubes coated with octadecylamine, N-acetylcysteine, doxycycline, and levofloxacin (6 pigs per group). No exogenous bacteria were inoculated into the pigs, pneumonia resulted from the pigs’ endogenous oral flora. Vital signs were recorded every 15 minutes and arterial blood gas measurements were obtained for the duration of the experiment. Pigs were sacrificed either after completion of 72 hours of mechanical ventilation or just prior to hypoxic arrest. Lungs, trachea, and endotracheal tubes were harvested for analysis to include bacterial counts of lung, trachea, and endotracheal tubes, lung wet and dry weights, and lung tissue for histology. ResultsPigs ventilated with coated endotracheal tubes were less hypoxic, had less bacterial colonization of the lungs, and survived significantly longer than pigs ventilated with uncoated tubes. Octadecylamine-N-acetylcysteine-doxycycline-levofloxacin coated endotracheal tubes had less bacterial colonization than uncoated or octadecylamine-N-acetylcysteine coated tubes. ConclusionEndotracheal tubes coated with antimicrobial lipids plus mucolytic and antimicrobial lipids with antibiotics plus mucolytic reduced bacterial colonization of pig lungs after prolonged mechanical ventilation and may be an effective strategy to reduce ventilator-associated pneumonia.

Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life.

Newborns and unvaccinated infants, compared to other age groups, are more susceptible to pertussis infection, manifesting severe symptoms leading to a higher mortality. The recent increase in pertussis cases demands more effective strategies to overcome this major health problem. In parallel with maternal-immunization, neonatal-immunization (NI) is a strategy needing revision. Here, using the intranasal-challenge-mouse-model we evaluated the protective capacity of NI in both naïve-mice and those with maternally acquired immunity. We tested our acellular-vaccine-candidate based on outer-membrane-vesicles derived from Bordetella pertussis (OMVP) that induces Th2-profile but also the recommended Th-profile for protection: Th1/Th17-profile and CD4 T-memory-cells that reside in the lungs. Commercial acellular-vaccine (aP) and whole cell-vaccine (wP) inducing mainly Th2-profile and Th1-profile, respectively, were also tested. Analyzing the induced immunity and protection capability of NI included in 1- or 2-dose schedules with the same or different types of vaccine, we detected that the aP-vaccine administered in either single- or 2-dose schedules protected against sublethal B. pertussis infection. Schedules consisting of doses of aP neonatally and of OMVP or wP vaccine during infancy greatly reduced bacterial lung colonization while inducing the highest levels of high-avidity anti-pertussis toxin (PTx) IgG. That OMVP or wP neonatal dose did not interfere with the protection of transferred maternal immunity was especially encouraging. Moreover, OMVP- or wP used as a neonatal dose enhanced the quality of the humoral immune response in immunized pups. Antibodies generated by OMVP-or wP-vaccinated mice born to aP-immunized mothers were of higher avidity than those from mice that harbored only maternal immunity; but when mothers and neonates were immunized with the same aP-vaccine, the humoral response in the neonates was partially suppressed through the blunting of the level of anti-PTx IgG induced by the neonatal aP dose. These results demonstrated that neonatal immunization is a possible strategy to be considered to improve the current pertussis epidemiology. For neonates without maternal-immunity, mixed-vaccination schedules that include the aP- and OMVP-vaccines appear to be the most appropriate to induce protection in the pups. For offspring from immune mothers, to avoid blunting-effect, NI should be carried out with vaccines other than those applied during pregnancy.

Murine Acute Pneumonia Model of Pseudomonas aeruginosa Lung Infection.

Animal infection models play significant roles in studying bacterial pathogenic mechanisms, host pathogen interaction as well as evaluating drug and vaccine efficacies. We have been utilizing an acute pneumonia model to study bacterial colonization in lungs and assess virulence to the host by determination of bacterial loads and survival assays, as well as examine the bacterial gene expression in vivo. Additionally, the host's immune response to the pathogen can be explored through this infection model.

Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode.

BackgroundBinge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system’s ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo.Principal findingsIn this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2% v/v alcohol in vitro.ConclusionsOur results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.

Reactivating Immunity Primed by Acellular Pertussis Vaccines in the Absence of Circulating Antibodies: Enhanced Bacterial Control by TLR9 Rather Than TLR4 Agonist-Including Formulation.

Pertussis is still observed in many countries despite of high vaccine coverage. Acellular pertussis (aP) vaccination is widely implemented in many countries as primary series in infants and as boosters in school-entry/adolescents/adults (including pregnant women in some). One novel strategy to improve the reactivation of aP-vaccine primed immunity could be to include genetically- detoxified pertussis toxin and novel adjuvants in aP vaccine boosters. Their preclinical evaluation is not straightforward, as it requires mimicking the human situation where T and B memory cells may persist longer than vaccine-induced circulating antibodies. Toward this objective, we developed a novel murine model including two consecutive adoptive transfers of the memory cells induced by priming and boosting, respectively. Using this model, we assessed the capacity of three novel aP vaccine candidates including genetically-detoxified pertussis toxin, pertactin, filamentous hemagglutinin, and fimbriae adsorbed to aluminum hydroxide, supplemented—or not—with Toll-Like-Receptor 4 or 9 agonists (TLR4A, TLR9A), to reactivate aP vaccine-induced immune memory and protection, reflected by bacterial clearance. In the conventional murine immunization model, TLR4A- and TLR9A-containing aP formulations induced similar aP-specific IgG antibody responses and protection against bacterial lung colonization as current aP vaccines, despite IL-5 down-modulation by both TLR4A and TLR9A and IL-17 up-modulation by TLR4A. In the absence of serum antibodies at time of boosting or exposure, TLR4A- and TLR9A-containing formulations both enhanced vaccine antibody recall compared to current aP formulations. Unexpectedly, however, protection was only increased by the TLR9A-containing vaccine, through both earlier bacterial control and accelerated clearance. This suggests that TLR9A-containing aP vaccines may better reactivate aP vaccine-primed pertussis memory and enhance protection than current or TLR4A-adjuvanted aP vaccines.

Antibacterial Micelles with Vancomycin-Mediated Targeting and pH/Lipase-Triggered Release of Antibiotics

Antibiotic delivery systems play an important role in increasing the efficacy while reducing the off-target toxicity and antibiotic resistance. Though bacterial infections share pathophysiological pathways similar to tumor tissues, few delivery systems have achieved bacterial targeting and on-demand release of antibiotics. In the current study, amphiphilic poly(ethylene glycol)-poly(ε-caprolactone) (PECL) copolymers are conjugated with vancomycin (VAN) as targeting ligands via pH-cleavable hydrazone bonds to obtain micelle carriers (Van-hyd-PECL). Subsequently, ciprofloxacin (CIP) is encapsulated to obtain Van-hyd-PECL/Cip micelles with an average size of 77 nm and a CIP loading amount of 4.5%. The poly(ethylene glycol) shells and the extension of VAN moieties on the micelle surface enhance the blood circulation and selective recognition of bacteria. The deshielding of VAN shells under acidic conditions disrupts the hydrophobic/hydrophilic balance leading to an increase in micelle sizes, which facilitates the degradation of poly(ε-caprolactone) by lipase overexpressed in the infection site and the release of encapsulated CIP for bacterial destruction. The micelle treatment has improved the survival of Pseudomonas aeruginosa-infected mice and reduced the bacterial burdens and alveolar injuries in lungs, compared with free drugs and micelles without inoculation of VAN moieties. Three doses of Van-hyd-PECL/Cip micelles further extend the animal survival, decrease the bacterial colonization in lungs, and almost restore the normal alveolar microstructure. In this regard, this study has demonstrated a strategy to enhance the bacterial targeting of micelles via an antibiotic (VAN) and to sequentially trigger the release of antibiotics (VAN and CIP) at the infection site.

Immunogenicity and protective efficacy of recombinant iron superoxide dismutase protein from Bordetella pertussis in mice models

Whooping cough (pertussis) is a highly contagious respiratory infection caused by Bordetella pertussis. Although availability of effective pertussis vaccines reportedly decreases the incidence of the disease, B. pertussis circulation in populations has not been eliminated. Thus, it is necessary to find new protein candidates with greater immune protective capacities than the currently available acellular pertussis vaccines. In this study, iron superoxide dismutase (FeSOD) gene (sodB) was cloned, expressed in Escherichia coli and recombinant FeSOD protein thence purified. The recombinant protein (rFeSOD) was formulated with aluminum hydroxide (Alum) or monophosphoryl lipid A (MPLA) and injected intraperitoneally to immunize mice, after which IgG1, IgG2a and IFN-γ titers were measured to assess humoral and cellular responses, respectively, to these immunizations. The extent of bacterial colonization in lungs of intranasally challenged mice was determined 5, 8 and 14 days post-challenge. IgG1 and IgG2a responses were significantly stronger in mice that had been immunized with rFeSOD-MPLA than in those that had received rFeSOD-Alum (P < 0.05). Additionally, IgG2a titers were higher in mice vaccinated with recombinant protein FeSOD (rFeSOD) formulated with MPLA, especially after the second immunization. Immunization with rFeSOD-MPLA also provided a modest, but significant decrease in bacterial counts in lungs of mice (P < 0.05). Antigen specific-IFN-γ responses were significantly stronger in the group vaccinated with rFeSOD-MPLA, which could account for the lower bacterial counts. These findings suggest that rFeSOD protein formulated with MPLA has potential as an acellular pertussis vaccine candidate component.

Sugar administration is an effective adjunctive therapy in the treatment ofPseudomonas aeruginosapneumonia

Treatment of acute and chronic pulmonary infections caused by opportunistic pathogen Pseudomonas aeruginosa is limited by the increasing frequency of multidrug bacterial resistance. Here, we describe a novel adjunctive therapy in which administration of a mix of simple sugars-mannose, fucose, and galactose-inhibits bacterial attachment, limits lung damage, and potentiates conventional antibiotic therapy. The sugar mixture inhibits adhesion of nonmucoid and mucoid P. aeruginosa strains to bronchial epithelial cells in vitro. In a murine model of acute pneumonia, treatment with the sugar mixture alone diminishes lung damage, bacterial dissemination to the subpleural alveoli, and neutrophil- and IL-8-driven inflammatory responses. Remarkably, the sugars act synergistically with anti-Pseudomonas antibiotics, including β-lactams and quinolones, to further reduce bacterial lung colonization and damage. To probe the mechanism, we examined the effects of sugars in the presence or absence of antibiotics during growth in liquid culture and in an ex vivo infection model utilizing freshly dissected mouse tracheas and lungs. We demonstrate that the sugar mixture induces rapid but reversible formation of bacterial clusters that exhibited enhanced susceptibility to antibiotics compared with individual bacteria. Our findings reveal that sugar inhalation, an inexpensive and safe therapeutic, could be used in combination with conventional antibiotic therapy to more effectively treat P. aeruginosa lung infections.

Antimicrobial Coated Endotracheal Tube and Clearance Devices to Prevent Secretion Accumulation in Mechanically Ventilated Patients

Endotracheal tubes (ETT) of intubated patients are constantly challenged with abundant bacteria-laden secretions. These bacteria may rapidly form a well-organized structure, referred to as biofilm, on the inner surface of the ETT. Secretions become very tenacious and are difficult to clear. However, bacteria and secretions can detach spontaneously or become dislodged by suction catheters and enter the lungs, providing a source of infection. Recently, several strategies have been developed to prevent accumulation of mucus and bacterial colonization of the respiratory circuit. In this review, we summarize published studies on antimicrobial ETT-coated and clearance devices. Numerous antimicrobial-impregnated ETTs have been designed with bactericidal/static properties to prevent adhesion of bacteria on ETT surfaces. Several in vitro experiments and animal-studies have shown success in the prevention of bacterial colonization through the use of these specialized ETTs. At present, only two ETT coatings, silver-hydrogel and silver-sulfadiazine in polyurethane, have been tested in clinical trials. Both coatings have been shown to prevent/lower bacterial colonization of the ETT, while only the silver-hydrogel coating decreased bacterial colonization of lungs in a large multicenter study. Another innovative approach is to reduce contaminated-secretions in the ETT-lumen with novel medical devices designed to retrieve accumulated-mucus from the ETT. The mucus shaver and the mucus slurper are two devices intended to reduce loaded-bacteria secretions from within the ETT. While experimental and preliminary clinical trials are promising, there are no large clinical trials showing outcome benefits. Keywords: Bacterial colonization, endotracheal tube, mechanical ventilation, ventilator associated pneumonia.

MudPIT analysis of released proteins inPseudomonas aeruginosalaboratory and clinical strains in relation to pro-inflammatory effects

Pseudomonas aeruginosa (Pa) is the most common virulent pathogen contributing to the pathogenesis of cystic fibrosis (CF). During bacterial lung colonization, the products of its metabolism are released in the extracellular space contributing to the pathogenic events associated with its presence. To gain insights on the mechanisms involved in the Pa pathogenesis we focused our attention on proteins released by Pa using a MudPIT approach combined with cell biology assays. Conditioned medium (CM) collected under aerobic and microaerobic conditions from Pa clinical strains (in early and late colonization), unlike the laboratory strain, induced expression of IL-8 mRNA in CF airway epithelial cells. We have identified proteins released by clinically relevant Pa strains, focusing on the pro-inflammatory effects as metalloproteases (MMPs). In fact, their expression pattern was associated with the highest pro-inflammatory activity measured in the early clinically isolated strain. The relation was further supported by the result of the analysis of a larger and independent set of Pa isolates derived from sporadically and chronically infected CF patients: 76% of sporadic samples expressed protease activity (n = 44), while only 27% scored positive in the chronically infected individuals (n = 38, p < 0.0001, Fisher's exact test). Finally, looking for a possible mechanism of action of bacterial MMPs, we found that CM from early clinical isolates can cleave CXCR1 on the surface of human neutrophils, suggesting a potential role for the bacterially released MMPs in the protection of the pathogen from the host's response.

Resource usage in outpatient care and reimbursement for cystic fibrosis in Germany

Objective of this study is to assess and evaluate resource use in outpatient treatment in Germany and to compare it with remuneration. Outpatient treatment was evaluated in seven different centers for pediatric and adult CF patients. Data were recorded during one representative month in 2006. A micro-costing approach was used to value resource use data. For outpatient treatment mean costs (excluding drugs) of 488 € per patient per quarter occurred. Correlation analyses identified significant cost drivers including age and co-morbidities (pancreatic insufficiency, hepatobiliary complications, lung function capacity, or bacterial lung colonization). Remuneration covered only 51% of the total costs (252 € per patient/quarter). As the human resources available to these centers today are already below the requirements set by the European consensus for standards of CF care it will be important for a high level of patient care to reach a cost-covering remuneration scheme.

Prevention of Endotracheal Tube Biofilm Formation in Intubated Critically Ill Patients

Endotracheal tubes (ETT) of intubated patients are constantly challenged with abundant bacteria-laden secretions. Quickly those bacteria may organize in a well-organized structure (biofilm) which is difficult to eradicate. Fragments can detach spontaneously or become dislodged by suction catheters and enter the lungs representing a source of infection. Recently several strategies have been developed to prevent bacterial biofilm formation and secretion accumulation. In this review we summarized published studies on ETT-biofilm prevention. Numerous antimicrobial-impregnated ETT have been designed to provide either bactericidal/static properties, or to prevent adhesion of bacteria on its surface. In vitro experiments and animal-studies showed several success rates in the prevention of bacterial colonization of the tube. Up to now, only two coatings, silver-hydrogel and silver-sulfadiazine in polyurethane, have been tested in clinical trials. Both proved to prevent/lower bacterial colonization of the ETT, while only the silver-hydrogel coating decreased bacterial colonization of lungs in a large multicenter study. Another innovative approach is to reduce contaminated-secretions in the ETT-lumen with novel medical devices designed to retrieve accumulated-mucus from the ETT/trachea. The mucus shaver and the mucus slurper are intended to reduce loaded-bacteria secretions from within the ETT/trachea. While experimental studies are promising, no clinical trials have been performed yet to prove this novel concept. Keywords: Biofilm, endotracheal tube, mechanical ventilation, ventilator associated pneumonia

Long-term flaxseed oil supplementation diet protects BALB/c mice against Streptococcus pneumoniae infection

Intense host immune response to infection contributes significantly to the pathology of pneumococcal pneumonia. Therefore, the regulation of host immune response is critical for the successful outcome of pneumonia in such patients. The aim of the present study was to investigate the effect of n-3 PUFA, i.e. flaxseed oil supplementation for short (4 weeks) as well as long (9 weeks) term, on the course of S. pneumoniae D39 serotype 2 infection in mice. The efficacy of flaxseed oil supplementation was investigated in terms of survival of animals and production of various inflammatory molecules (malondialdehyde, myeloperoxidase, nitric oxide) in the lung homogenate of animals. This was correlated with bacteriological and histopathological parameters. The immunomodulation was studied in terms of cytokines in the lungs following infection with Streptococcus pneumoniae. Results suggest that long-term flaxseed supplementation protected the mice against bacterial colonization of lungs with Streptococcus pneumoniae with reduced histopathological involvement of lung tissue. Moderate pneumonia was observed in supplemented, infected mice compared to severe pneumonia seen in control mice. This was accompanied by decreased inflammatory markers (malondialdehyde, myeloperoxidase, nitric oxide) as the disease progressed. In addition, difference in the levels of pro-inflammatory (TNF-alpha and IL-1beta) and anti-inflammatory (IL-10) cytokines was observed in the flaxseed fed animals. On the contrary, short-term supplementation did not show such an effect on lung colonization.

Protection against pneumococcal pneumonia in mice by monoclonal antibodies to pneumolysin.

Pneumolysin (PLY) is an important virulence factor of Streptococcus pneumoniae. We examined the ability of three murine monoclonal antibodies (MAbs) to PLY (PLY-4, PLY-5, and PLY-7) to affect the course of pneumococcal pneumonia in mice. The intravenous administration of antibodies PLY-4 and PLY-7 protected the mice from the lethal effect of the purified toxin. Mice treated with PLY-4 before intranasal inoculation of S. pneumoniae type 2 survived longer (median survival time, 100 h) than did untreated animals (median survival time, 60 h) (P < 0.0001). The median survival time for mice treated with a combination of PLY-4 and PLY-7 was 130 h, significantly longer than that for mice given isotype-matched indifferent MAbs (P = 0.0288) or nontreated mice (P = 0.0002). The median survival time for mice treated with a combination of three MAbs was significantly longer (>480 h) than that for mice treated with PLY-5 (48 h; P < 0.0001), PLY-7 (78 h; P = 0.0007), or PLY-4 (100 h; P = 0.0443) alone. Similarly, the survival rate for mice treated with three MAbs (10 of 20 mice) was significantly higher than the survival rate obtained with PLY-5 (1 of 20; P = 0.0033), PLY-4 (2 of 20; P = 0.0138), or PLY-7 (3 of 20; P = 0.0407) alone. These results suggest that anti-PLY MAbs act with a synergistic effect. Furthermore, MAb administration was associated with a significant decrease in bacterial lung colonization and lower frequencies of bacteremia and tissue injury with respect to the results for the control groups.

Protection against Klebsiella pneumoniae induced lobar pneumonia in rats with lipopolysaccharide and related antigens

The immunoprotective role of lipopolysaccharide and related antigens from Klebsiella pneumoniae was studied in a lobar pneumonia model developed in rats. Various antigens were obtained by different chemical treatments of the lipopolysaccharide. All these antigens (purified lipopolysaccharide, reduced lipopolysaccharide, lipopolysaccharide--bovine serum albumin complex, and lipid A--bovine serum albumin complex were tested for pyrogenicity and the Shwartzman reaction. The lipopolysaccharide and the various related antigens were pyrogenic and elicited a positive Shwartzman reaction at high concentrations. However, at low concentrations, the same preparations did not show any side effects. All these antigens, on the other hand, were protective against bacterial challenge in Klebsiella pneumoniae induced lobar pneumonia in rats, as the bacterial colonization of lungs in the immunized animals was significantly lower when compared with the controls. The alveolar macrophages from these animals also showed significantly more uptake of Klebsiella pneumoniae as compared with those obtained from control animals.