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Biomedical subjects

A Fomsgaard

Publications and source records attributed to A Fomsgaard.

At least 19 recordsLinked to original sources
PubMed1996

Prevalence of antibodies to lipid A in Danish cattle.

A cross-sectional study was performed on the occurrence of IgG antibodies to lipid A of the Gram-negative bacterial lipopolysaccharide (LPS, endotoxin) on serum of 2272 cattle distributed on 19 Danish dairy herds. The relationship between the concentration of antibodies to lipid A (ALI) and age, herd, pregnancy rate and occurrence of mastitis, bovine virus diarrhoea (BVD), reproductive and digestive disorders, diarrhoea, pneumonia, foot disorders, various infections and traumatic udder lesions was investigated. ALI generally was low in calves and increased during their first 1.5 years of life to a steady state, which could be altered by the occurrence of disease. There were significant differences in the mean ALI among the herds (P < 0.001). High ALI was associated with a low herd pregnancy rate, to preceding occurrence of mastitis (P < 0.048), BVD (P < 0.01), reproduction diseases (P < 0.041) and digestion disorders (P < 0.064) in animals older than 2 years. The calf mortality rate was not associated to ALI and there was no correlation between the ALI in calves and their dams. The occurrence of high ALI levels on a herd basis may be an indication of increased challenge or enhanced immunological defense to Gram-negative bacteria or endotoxin.

Aging↗
PubMed1995

[Genetic immunization--"the biological equivalent of cold fusion"?].

Genetic immunization is a new vaccine technology, where antigen encoding DNA plasmids are directly injected into muscle or skin with the purpose of eliciting an immune response to the gene product. The gene products are correctly glycosylated, folded and expressed by the host cell. This is an advantage when the antigens are difficult to obtain in the desired purity, amount or correctly glycosylated form or when only the genetic sequences are known e.g. HCV. The DNA plasmids are injected into muscles or delivered coated onto gold microparticles into the skin by a particle bombardment device, a "gene gun". Genetic immunization has demonstrated induction of both a specific humoral but also a more broadly reacting cellular immune response in animal models of cancer, mycoplasma, TB, malaria, and many virus infections including influenza and HIV. Thus, the DNA vaccine mimics a live vaccine without the biohazard. Many animal species have responded to genetic immunization and gene vaccine has also been used to induce a desired immuneresponse in patients with cancer and HIV. The technique was first described in 1992 but is developing fast. This review describes the history and principle of the technology, its advantages, problems and possible applications.

Antibody Formation↗
PubMed1995

Prevalence and antibiotic sensitivity of Danish versus other European bacterial isolates from intensive care and hematology/oncology units.

The prevalence and antibiotic sensitivity patterns of bacteria collected consecutively from medical and surgical intensive care units (ICUs) and from hematology/oncology units in nine hospitals in Denmark were determined and compared to data collected simultaneously in 12 other European countries. Bacterial isolates from 794 Danish patients were tested and compared to 8,625 isolates from European patients. The minimal inhibitory concentrations of eight different antibiotics were determined using a microdilution plate. Similar to findings in European countries, the most common source of bacterial isolates in Danish units was the respiratory tract (49%), followed by blood (18%), urinary tract (14%) and surgical wounds (10%). Staphylococcus aureus was the most prevalent respiratory organism in Danish units, whereas Enterobacteriaceae and Pseudomonas aeruginosa dominated in other countries. In blood, Escherichia coli was most prevalent in Denmark while coagulase-negative staphylococci were predominant in other countries. Urinary tract isolates were dominated by Escherichia coli in both Denmark and the other countries, but Enterococcus faecalis and Pseudomonas aeruginosa were more frequently isolated in the other countries. Staphylococcus aureus was the most frequent wound isolate in Denmark, while Enterobacteriaceae other than Escherichia coli dominated in other European countries. Thus, in Denmark Escherichia coli and Staphylococcus aureus, followed by Pseudomonas aeruginosa and Klebsiella spp. (from ICUs) or Enterococcus spp. and Klebsiella spp. (from hematology/oncology units), are the most prominent pathogens in these units today. Indicator organisms of antibiotic consumption (Pseudomonas aeruginosa and methicillin-resistant coagulase-negative staphylococci and Staphylococcus aureus) were more frequent in other European countries than Denmark. In general the Danish isolates were more sensitive to antibiotics than the European isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1995

Receptor function of CD4 structures from African green monkey and pig-tail macaque for simian immunodeficiency virus, SIVsm, SIVagm, and human immunodeficiency virus type-1.

Differences in kinetics of infection, cellular tropism, and cytopathology of SIV and HIV appear to depend on both viral and host factors. We investigated the role of critical CD4 structures from African green monkeys (AGM) a natural SIV host, from pig-tailed macaques (PT) an unnatural SIV host, and from humans, as well as the role of species-specific cellular factors involved in the tropism, kinetics of infection, and cytopathic effects of several SIV and HIV-1. Critical regions of the PT macaque and AGM CD4 genes (V1, V1J1, and V1J1V2J2) were stably expressed as chimeras with the human CD4 gene in human (HeLa and 293) and macaque (CMMT) cell lines. CD4 expressing cell lines were used for infection studies with cell-free SIVsm, SIVmac, SIVsmmPBj, SIVagm, and HIV-1. Results show that both PT CD4 and AGM CD4 supported infection with comparable infection kinetics by all SIV or HIV-1 strains tested. Although structural analysis predicted a major change in secondary structure of AGM CD4/CDR-3, these structural changes did not influence the degree of syncytia formation induced by several SIV and HIV-1. However, the cell line used to express the CD4 gene appeared to be a critical determinant of infection. Thus, SlV strains did not infect human cell lines regardless of the CD4 expressed in these cells. In contrast, HIV-1 did not infect any macaque cell line. This study demonstrates that the differences in CD4 structure among different primate species are clearly not responsible for differences in SIV and HIV infection kinetics, tropism, and cytopathology. However, species-specific factor(s), presumably expressed on the cell surface, markedly influences the ability of SIV or HIV to infect cells expressing CD4.

Amino Acid Sequence↗
PubMed1995

An easy microtiter assay for quantitation of cytokine induction by lipopolysaccharide (LPS) and activity of LPS-binding serum components.

Lipopolysaccharide (LPS, endotoxin) is a major inducer of cytokines, such as interleukin 1 (IL1), IL6, IL8 and tumor necrosis factor (TNF). A convenient microtiter assay was developed to measure such activity. LPS coated onto a plastic surface was used to stimulate purified human mononuclear cells (MNC) in microtiter plates. Following stimulation the supernatants were assayed for presence of TNF by ELISA. Purified rough and smooth LPS from Pseudomonas aeruginosa gave a dose-dependent TNF release over a range of 0.1-1.0 microgram LPS/well. The assay was subsequently used to investigate the biological activity of anti-LPS antibodies and other LPS-specific serum components in sera from patients with cystic fibrosis (CF). As a group, sera from 10 CF patients chronically infected with P. aeruginosa did not affect the LPS-induced TNF release, while sera from normal controls inhibited this biological activity. When individual CF patients with or without chronic lung infection are considered, the antibodies appear to either enhance or inhibit the LPS-stimulated TNF release (range: 73-120%), while all antibodies from healthy controls inhibit the activity of LPS (range: 76-97%). Only a weak correlation (rho = 0.491, p = 0.037, n = 19) was found between the antibody titer in ELISA and the biological activity of sera. This new assay is suggested for convenient measurement of interference with cytokine induction from human MNC by patient or therapeutic anti-LPS antibodies and other LPS-specific serum components.

Antibodies, Bacterial↗
PubMed1995

Cloning and nucleotide sequence comparison of the groE operon of Pseudomonas aeruginosa and Burkholderia cepacia.

By alignment of GroEL amino acid sequences from four distantly related bacteria two highly conserved domains were identified. Two oligonucleotides complementary to the conserved domains were designed based on the preferred Pseudomonas aeruginosa codon usage. The primers were used in the PCR to amplify a 900-base fragment of the P. aeruginosa groEL gene. The fragment was sequenced and the partial GroEL sequence was expanded by vectorette PCR upstream and downstream to cover the complete P. aeruginosa groE operon. The same technique was used to sequence the Burkholderia cepacia (formerly Pseudomonas cepacia) groE operon and the region immediately upstream of groES. The B. cepacia groE operon is preceded by typical -10 and -35 heat shock expression signals. A total of 2041 and 2139 bp was sequenced from P. aeruginosa and B. cepacia respectively. Each revealed two open reading frames encoding two proteins with a predicted molecular mass of 10 and 57 kDa, corresponding to GroES and GroEL respectively. The GroEL proteins show an interspecies amino acid homology of 71%, and 73% with E. coli GroEL. Both GroEL proteins are 52% homologous to the corresponding human mitochondrial GroEL protein. The sequence data confirm the existence of highly conserved structures, which could be functionally important for the concerted action of GroEL and GroES in the folding and assembly of other proteins, and possibly in the initiation of autoimmune diseases.

Adolescent↗
PubMed1995

Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization.

In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis, we investigated the possibility of preventing chronic lung inflammation or decreasing the progression of the infection. We compared the lethality, pathology, bacterial clearance, and immunogenicity after stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated with either E. coli LPS or P. aeruginosa sonicate. Four and two weeks prior to challenge other rats were vaccinated with either E. coli LPS or P. aeruginosa sonicate. Controls did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p = 0.02) or vaccinated with P. aeruginosa sonicate (p = 0.03) as compared to controls. The histopathology of the surviving rats showed an acute inflammation dominated by polymorphonuclear leukocytes (PMNs), but the offending bacteria were not completely eliminated in any group. The increased survival was probably due to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival but not to prevent the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria.

Animals↗
PubMed1994

[Biofilm, foreign bodies and chronic infections].

Most bacteria occur in the environment as sessile cells adhering to a surface, whereas a minority exists as free floating (planktonic) cells. Biofilms consist of microcolonies embedded in a polysaccharide matrix produced by the bacteria. This polysaccharide slime protects the bacteria against hostile environmental factors. Planktonic daughter cells are liberated from the surface of biofilms and may colonize new surfaces and subsequently produce new biofilms. Biofilms are often consortia of several different bacterial species. The normal microflora on the skin or on the mucous membranes in the human body occurs as a biofilm, which is removed by the shedding of old cells and by the excretion of mucus. Subsequently new cells and new mucus are colonized by biofilm forming bacteria without giving rise to any symptoms. When body surfaces with a normally occurring microflora (A) are connected by means of an implanted foreign body with body surfaces or tissue compartments without a microflora (B) e.g. bronchi, gall bladder, peritoneum, veins, then a translocation of the normal microflora from (A) to (B) may easily occur leading to acute infection, formation of new biofilms on the implanted foreign body and induction of inflammation in the environment of this biofilm. Chronic bacterial infections are frequently caused by biofilm producing bacteria and the pathogenesis of the tissue damage is dominated by a persistent immune complex mediated inflammation. Bacteria growing in biofilms cannot be eradicated by antibiotics and biofilms resist the immunological and non-specific defence mechanisms of the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted.

A total of 162 anti-HAV-negative healthy adults were immunized with a single high dose (1440 ELISA units = 1 ml) of inactivated hepatitis A vaccine and a booster was given at month 6. Antibodies were measured after modification of a commercial ELISA kit, enabling quantification of titres down to 6 mIU ml-1. After 14 days, 96% of vaccinees had positive anti-HAV titres (> 20 mIU ml-1), and after 30 days all vaccinees had seroconverted. The geometric mean titres were 150 mIU ml-1 and 380 mIU ml-1 respectively. The booster dose at month 6 elicited a dramatic (25-fold) increase in antibody titres from 125 to 3090 mIU ml-1. Thus a single dose may be a convenient alternative to immunoglobulin for inducing rapid seroprotection, with a booster dose at month 6 ensuring long-lasting protection.

Adolescent↗
PubMed1994

Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection.

Pseudomonas aeruginosa is the predominant pathogen in patients with cystic fibrosis (CF). To study the possibility of preventing lung inflammation and decreasing the progression of the infection by vaccination, we have developed a rat model of chronic P. aeruginosa lung infection. Rats were immunized with P. aeruginosa whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P < 0.05) and microscopic (mean score, 2.0 versus 2.1 to 2.8) pathologic abnormalities were less severe in the control rats injected with sterile saline than in the immunized rats and the IFA group. The more severe lung abnormalities observed in immunized rats could be due to the result of immune complex-mediated lung tissue damage. The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IFA group and in the immunized rats had changed from an acute-type inflammation to a chronic-type inflammation dominated by mononuclear leukocytes and scattered granulomas. Cross-reacting antibodies were induced by the two alginate vaccines, and most immunized animals developed a significant (P < 0.001) antibody titer elevation (in enzyme-linked immunosorbent assay) of the immunoglobulin M (IgM), IgG, and IgA classes against the homologous antigens. The bacterial clearance was significantly (P < 0.05) more efficient in most immunized rats than in the control rats given sterile saline. The present study shows that none of the vaccines could completely prevent chronic lung inflammation 4 weeks after challenge. However, the changed pathologic condition in immunized rats to a chronic-type inflammation might be of great benefit in future management of CF patients since the developing lung tissue damage has been shown to be caused by polymorphonuclear leukocyte-released elastase.

Animals↗
PubMed1993

[Translocation and multiple organ failure].

A review of bacterial translocation and multiple organ failure (MOF) is presented. Splanchnic ischaemia plays a central role in the development of MOF, but the exact mechanism of translocation is unclear. The concentration of endotoxins and bacteria in the gut is high. The critically ill patient is often treated with antibiotics with a broad antibacterial spectrum and overgrowth of Gram negative bacteria will take place in the gut favouring the translocation phenomenon. The regime of selective gut decontamination is discussed. Regional and systemic oxygen kinetics together with metabolic markers are important in detecting splanchnic ischaemia. Hepatic vein catheterisation and gastric mucosa pHi are discussed. The regional inflammation in the gut is often initiated by endotoxins, which stimulate the cytokines IL-1, IL-6 and TNF. Another important factor that can accentuate inflammation of the gut is reperfusion injury. A proposal for treatment of splanchnic ischaemia and translocation is discussed i.e.: optimizing central haemodynamic parameters, optimizing the regional microcirculation, treatment with antibodies to endotoxins, gut decontamination and early enteral nutrition. When splanchnic hypoperfusion is detected it cannot be ignored. It may be possible to correct the hypoperfusion with early gastrointestinal resuscitation and to thereby reduce the duration and mortality of MOF. The above mentioned suggestions are all very demanding of resources, but have to be considered in gut directed therapy.

Anti-Bacterial Agents↗
PubMed1993

Cytokines in sputum and serum from patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection as markers of destructive inflammation in the lungs.

The presence of interleukin (IL)-1 receptor antagonist (IRAP) in plasma and sputum from patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection was investigated together with IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF) in a cross-sectional study. All cytokines were assayed by ELISAs. High concentrations of IRAP, IL-1 alpha, IL-1 beta, IL-6, and TNF in sputum samples and low or nondetectable levels of circulating cytokines were frequently found. Increased concentrations of plasma IRAP are positively correlated with decreasing pulmonary function. In a longitudinal study of serum IRAP, a higher level of IRAP was detected in a group of patients with poor pulmonary function compared to a group with good pulmonary function.

Adolescent↗
PubMed1993

Complement activation by Pseudomonas aeruginosa biofilms.

In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm mode of growth. In this study we investigated the role of biofilms in activation of complement, a major contributor to the inflammatory process. Complement activation by P. aeruginosa was examined in a complement consumption assay, production of C3 and factor B conversion products assessed by crossed immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact biofilms was submaximal. Factor B conversion was of low magnitude indicating the importance of the classical pathway. Complement activation by P. aeruginosa was inhibited by polymyxin B indicating that lipopolysaccharide (LPS) was the main mediator of complement activation. Immune complexes and massive influx of neutrophils are known to cause inflammatory changes in the lungs. P. aeruginosa persisting in biofilms may contribute to the constant inflammation taking place in the lungs of CF patients.

Chemotaxis, Leukocyte↗
PubMed1993

Enhancement of lipopolysaccharide-induced tumor necrosis factor secretion by hyperimmune serum from chronic infected patients.

Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have a very high load of endotoxins in their lungs. However, sepsis practically never occurs in this group of patients and the presence of tumor necrosis factor (TNF)-alpha (one of the mediators of septic shock) in serum from chronically infected CF patients is contentious. The purpose of this study was to investigate the effect of hyperimmune serum from patients with CF on lipopolysaccharide (LPS, endotoxin)-induced TNF secretion from human peripheral blood mononuclear cells (PBMC). PBMC were purified from healthy donors and stimulated with a mixture of purified LPS from P. aeruginosa and serum from chronically infected CF patients or healthy controls. TNF in the cell supernatants was detected by an enzyme-linked immunosorbent assay method. CF sera showed a pronounced potentiating effect on TNF secretion from human PBMC induced by LPS from P. aeruginosa. In comparison, serum from healthy controls did not have this effect. By contrast, CF serum and serum from healthy controls showed only little potentiating effect when using LPS from Salmonella abortus equi at concentrations above 0.01 microgram/ml per 2 x 10(6) PBMC. This indicates a specific interaction between P. aeruginosa LPS and CF serum which enhances TNF secretion. The TNF responses varied depending on the sera used in the preincubation with LPS, and correlated positively to the specific IgG, IgA, and IgM anti-P. aeruginosa LPS titers of the sera. However, since TNF is hardly detectable in sera from these patients another LPS- and/or TNF-inhibitory activity may be present in these sera.

Antigen-Antibody Complex↗
PubMed1993

Genetic variation of the SIVagm transmembrane glycoprotein in naturally and experimentally infected primates.

OBJECTIVE: An in-frame stop codon prematurely truncating the transmembrane glycoprotein (TMP) is a common feature of many simian immunodeficiency virus, African green monkey strain (SIVagm) molecular clones. The purpose of this study was to investigate the native form of the SIVagm TMP in a naturally infected African green monkey (AGM) and to study the fate of the stop codon following the passage of SIVagm in primates. DESIGN: Polymerase chain reaction was used to clone the entire intracellular portion of the TMP from: (1) peripheral blood mononuclear cells (PBMC) of the naturally infected AGM 155; (2) an isolate of SIVagm155 in rhesus PBMC and (3) PBMC from pig-tailed macaques and AGM experimentally infected with an SIVagm molecular clone encoding a truncated TMP. RESULTS: PBMC of the naturally infected AGM contained a 'swarm' of related virus genotypes that encoded a full-length TMP, whereas tissue-culture passage in rhesus PBMC resulted in a prematurely truncated form of the TMP. This premature stop codon persisted in PBMC of monkeys experimentally infected with an SIVagm molecular clone. Both macaques and AGM of same subspecies as AGM 155 (Cercopithecus pygerythrus) and other subspecies (C. aethiops and C. sabaeus) became infected with SIVagm155. Genetic drift of this region of env, as assessed by calculation of the nucleotide substitution/site/year rate, was similar to that of other retroviruses. CONCLUSIONS: The native form of the SIVagm TMP is a full-length gp40, similar to the SIV macaque (SIVmac) strain and HIV-1. However, passage of SIVagm in tissue culture can result in point mutations that introduce a premature stop codon. This stop codon persists during subsequent in vivo passage of SIVagm in primates. This contrasts with similar studies in macaques infected with SIVmac, in which reversion of the TMP stop codon was observed.

Amino Acid Sequence↗
PubMed1993

Antibodies from chronically infected cystic fibrosis patients react with lipopolysaccharides extracted by new micromethods from all serotypes of Pseudomonas aeruginosa.

Micromethods were developed to extract lipopolysaccharide (LPS, endotoxin) from single bacterial colonies of the 20 recognized Pseudomonas aeruginosa type strains. The appearance of these LPSs in polyacrylamide gel electrophoresis (PAGE) and their reactivity with serum of cystic fibrosis (CF) patients chronically infected with P. aeruginosa was studied. Silver staining of LPS after PAGE showed that 13 of the P. aeruginosa LPSs had high numbers of O-repeating units arranged in 1-4 clusters of banding. Low-molecular-weight LPS fractions were more prominent in six of the serotype strains, of which O:7 and O:14 appeared semi-rough. Corresponding immunoblots using the CF sera showed LPS patterns very similar to the silver-stained appearance, indicating an immune reaction to all P. aeruginosa LPS including that from the newly discovered O:18, O:19 and O:20. This was unexpected since only a few serotype strains (mostly O:3, O:6 and O:9) had been isolated from the patients. Absorption experiments using purified and chemically defined P. aeruginosa rough LPS and smooth LPS suggested these immune reactions were due to antibodies cross-reactive to core/lipid A as well as to lower molecular weight O-polysaccharides or "A-bands". However, in some cases O:3, O:6, and O:9 LPSs were also found to contain additional distinct O-epitopes. Immune recognition of various polyagglutinable P. aeruginosa LPSs seemed also to be caused by cross-reactive antibodies. The described microextraction methods, followed by PAGE and silver staining or immunoblotting, are easy and convenient techniques with which to study antibodies against LPS epitopes and to screen for LPS phenotypic appearance using only a few bacterial colonies from larger numbers of Gram-negative bacterial strains.

Antibodies↗
PubMed1993

Effect of a human IgG preparation rich in antibodies to a wide range of lipopolysaccharides on gram-negative bacterial sepsis in burned mice.

A human intravenous IgG preparation (Anti-LPS IgG) rich in antibodies to different lipopolysaccharides (LPS) and a normal human intravenous IgG (NIgG) were investigated for their ability to confer passive immunity. Both preparations were given at the time of infection (prophylaxis) or during sepsis (therapy) to burned mice with lethal infection induced by various clinically relevant gram-negative bacteria. When given at the time of infection both IgG preparations (5 mg/mouse) inhibited lethality induced by some bacteria (Pseudomonas aeruginosa serogroup G and B), but not others (Serratia marcescens, Klebsiella pneumonia, Proteus mirabilis), indicating a protection by by strain-specific antibodies. However, no significant protection was seen when mice were treated during sepsis. The range of specific antibody titers to the whole live bacteria and heat-killed (LPS-preserved) bacteria in the NIgG paralleled that of Anti-LPS IgG; however, the magnitude of the antibody titers did not accurately reflect the protective capacity in vivo. Thus, the exact specificity of the protective antibodies is still unknown. The protective effect of both IgG preparations was dose-dependent; at low IgG doses (0.5 mg/mouse) better protection was obtained with Anti-LPS IgG, whilst at higher doses (> or = 1 mg/mouse) both preparations exhibited identical effects. Low doses of either IgG preparation in combination with subtherapeutic doses of piperacillin significantly enhanced early survival (day 2 for NIgG and day 2 + 3 for Anti-LPS IgG) against P. aeruginosa, but the protective effect waned thereafter. We conclude that a strain-specific antibacterial effect in a compromised mouse infection model can be obtained by early passive immunization with human IgG from large plasma pools. It is suggested that Anti-LPS IgG or NIgG may be of benefit in some cases of gram-negative sepsis when administered as prophylaxis together with proper antibiotic treatment.

Animals↗