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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alveolar macrophages in AIDS patients have a marked increase in tumor necrosis factor release in active Pneumocystis carinii pneumonia. We have demonstrated that pentamidine, an aromatic diamidine currently used to treat AIDS-related P. carinii pneumonia, is an effective inhibitor of cellular tumor necrosis factor release from lipopolysaccharide-stimulated rat alveolar macrophages at concentrations greater than 10(-8) M. Inhibition of release is not dependent upon the continued presence of pentamidine in the culture medium during the release phase. In addition, this blockage occurs at neither the transcriptional level as determined by Northern blot analysis nor the translational level as determined by Western blot analysis. Timed addition studies suggest that pentamidine is targeting relatively early events following lipopolysaccharide administration. Pentamidine appears to alter early lipopolysaccharide-induced cellular processes associated with the release of tumor necrosis factor from macrophages.
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PMID:Modulation of tumor necrosis factor release from alveolar macrophages treated with pentamidine isethionate. 162 13

The high mortality associated with current therapeutic approaches to nosocomial pneumonia has motivated consideration of newer immunologic approaches to prevention or therapy of this infection. Serotype specific vaccines, hyperimmune immunoglobulins, and monoclonal antibodies have been developed for certain problematic pathogens. Pseudomonas aeruginosa has been the major focus of this approach, and trials of hyperimmune anti-Ps. aeruginosa globulins for treatment of pneumonia are underway. Broad-spectrum, anti-lipopolysaccharide antibody preparations have also been employed for prophylaxis of nosocomial pneumonia, but to date these trials have not been successful. Finally, anticytokine antibody therapy to reduce infection-initiated inflammatory lung damage is under consideration.
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PMID:Immunological perspectives in prevention and treatment of nosocomial pneumonia. 164 32

Soluble mediators such as tumor necrosis factor alpha (TNF-alpha) may be important in the pathogenesis of many chronic pulmonary infections. We examined the ability of Corynebacterium pseudotuberculosis, Pasteurella haemolytica, and ovine lentiviruses (OvLV) to induce TNF-alpha secretion by pulmonary alveolar macrophages (PAM). Bronchoalveolar lavage cells, composed of greater than 90% PAM, were obtained from normal sheep. Bronchoalveolar lavage cells were cultured for 2, 24, 48, 72, or 168 h in endotoxin-free RPMI medium (with 10% autologous serum) or in medium containing one of the following additives: lipopolysaccharide, 1-micron polystyrene beads, C. pseudotuberculosis, P. haemolytica, or one of two plaque-cloned OvLV, 85/28 or 85/34. Lipopolysaccharide, C. pseudotuberculosis, and P. haemolytica induced TNF-alpha activity in PAM cultures as early as 2 h after inoculation, as assessed by a colorimetric cytotoxicity assay. This activity could be blocked by rabbit anti-recombinant bovine TNF-alpha serum. In contrast, medium alone, polystyrene beads, and productive infection by OvLV did not induce TNF-alpha activity in PAM cultures. Bacterial pathogens which infect pulmonary macrophages may elicit the secretion of TNF-alpha within the lungs and lead to the cachectic state associated with chronic pneumonia.
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PMID:Differential induction of tumor necrosis factor alpha in ovine pulmonary alveolar macrophages following infection with Corynebacterium pseudotuberculosis, Pasteurella haemolytica, or lentiviruses. 165 61

We employed a Pseudomonas aeruginosa mouse pneumonia model to evaluate the ability of a murine monoclonal antibody (MAb) specific for the O-side chain of P. aeruginosa Fisher Immunotype-1 lipopolysaccharide (LPS) to achieve and sustain therapeutic levels in plasma and lung tissue, reduce bacterial populations in the lung, and prevent pneumonia-associated mortality. An IgG3 MAb (Y1-5A4) administered to mice i.v. over a dose range of 125-1,000 micrograms/mouse produced plasma and lung tissue levels at 2 hr of 61-507 micrograms/ml and 4.3-150 micrograms/g, respectively. The 1,000 micrograms MAb dose reduced bacterial counts in lung tissue (log10 cfu/g +/- S.D.) and blood (log10 cfu/ml +/- S.D.) 20 hr post-treatment (18 hr post-challenge) from 10.00 +/- 0.66 to 7.66 +/- 0.91 (P less than 0.01) and from 4.39 +/- 0.81 to less than 3.0, respectively. Administration of MAb to mice in doses of 125-500 micrograms 2 hr prior to a 3 x 50% lethal bacterial challenge produced significant protection against death, with a calculated 50% protective dose of 167 micrograms. Protection was noted following administration of 1,000 micrograms of MAb up to 6 hr after bacterial challenge (P less than 0.05, compared with untreated control). Histological examination of lung tissue from infected mice revealed less acute inflammation, necrosis, and hemorrhage in MAb-treated compared with untreated control animals and greater localization of Pseudomonas antigen within the phagocytic cells in alveolar space. These findings document the in vivo therapeutic efficacy of an LPS-specific IgG MAb in a murine model of acute P. aeruginosa pneumonia, based in part upon the achievability of effective MAb concentrations in plasma and lung tissue.
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PMID:Pharmacodynamic and protective properties of a murine lipopolysaccharide-specific monoclonal antibody in experimental Pseudomonas aeruginosa pneumonia in mice. 180 64

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.
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PMID:The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation. 182 45

A mixture of five IgM human monoclonal antibodies (MAbs) against lipopolysaccharide antigens of Pseudomonas aeruginosa, plus a human IgG1 MAb against exotoxin A, were studied in 12 noninfected patients and 8 patients with P. aeruginosa bacteremia or pneumonia (or both). The preparation was well tolerated over a dose range of 0.3-1.2 ml/kg (0.75-3.0 mg/kg IgM protein). After a single infusion of 1.2 ml/kg (3.0 mg/kg IgM protein), serum antibody titers were boosted into therapeutic range, with serum half-lives ranging from 34 to 99 h. Also, opsonophagocytic activity in serum rose more than 1 log10 for all but one antibody. In no patient was an immunologic response against the MAb preparation detected.
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PMID:Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients. 844 Sep 53

To elucidate the clinical significance of serum-sensitivity of respiratory pathogenic Pseudomonas aeruginosa (P. aeruginosa) strains, we examined serum-sensitivity of P. aeruginosa isolated from 16 patients with lower respiratory tract infections and clinical backgrounds of these patients. We also evaluated the virulence of four serum-resistant and four serum-sensitive P. aeruginosa strains in murine pneumonia model induced by intratracheal challenge, and the silver-stained profiles of purified lipopolysaccharide (LPS) from these strains. Serum-sensitive strains were isolated only from patients with chronic bronchitis, bronchiectasis, and diffuse panbronchiolitis colonized with P. aeruginosa, and rarely caused pneumonias, while serum-resistant strains caused pneumonias in some cases. Intratracheal challenge of mice with 5 x 10(7) cfu per mouse of a serum resistant strain caused fatal hemorrhagic pneumonia with bacteremia. In contrast, the same dose of a serum-sensitive strain provided non-fatal pneumonia without bacteremia. LD50 of serum-sensitive strains in a murine model of P. aeruginosa pneumonia were at least 2-10 times higher than those of serum-resistant strain. The LPS profiles of two serum-resistant strains and one serum-sensitive strain showed ladder-like patterns. The similar analysis demonstrated that one serum-sensitive strain was lack of ladder-like patterns. These data support that serum-sensitive P. aeruginosa strains are less virulent than serum-resistant P. aeruginosa strains in the lower respiratory tract, and serum sensitivity of P. aeruginosa strains is determined by the structure of the O-side chain of LPS; either lack of the O-side chain or the presence of sparse O-side chain.
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PMID:[Serum sensitivity of Pseudomonas aeruginosa isolated from sputum as a virulence factor in the lower respiratory tract]. 191 Jan 22

Cirrhotic rats have decreased pulmonary bactericidal activity and increased bacteremia after experimental pneumococcal pneumonia. To determine if this finding is due to impaired pulmonary recruitment of polymorphonuclear leukocytes (PMNL), bronchoalveolar lavage (BAL) was done on cirrhotic and normal rats after transtracheal challenge with pneumococcal types 3 and 1. Mean absolute numbers of recruited PMNL in BAL fluid (BALF) at 2, 4, 6, 8, and 24 h after 10(7) cfu of type 3 challenge were similar in cirrhotic and normal rats. In both groups, lower numbers of PMNL were recruited after challenge with 10(5) cfu of type 3. Type 1 pneumococci stimulated recruitment of similar mean absolute numbers of PMNL (x10(7] in BALF (cirrhotics vs. normals) at 24 h after challenges with 10(5) cfu (0.3 +/- 0.1 vs. 0.3 +/- 0.1) and 10(7) cfu (2.9 +/- 1.3 vs. 2.8 +/- 0.7). Peripheral blood PMNL from cirrhotic and normal rats did not differ in adherence to nylon wool columns or in chemotaxis toward lipopolysaccharide-activated normal rat serum. Thus the impaired pulmonary defense against pneumococcal pneumonia in cirrhosis is not due to deficient pulmonary PMNL recruitment.
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PMID:Pulmonary recruitment, adherence, and chemotaxis of neutrophils in a rat model of cirrhosis and pneumococcal pneumonia. 195 20

Monoclonal antibodies (MAbs) directed against the 37.5-kDa outer membrane protein were produced by fusing myeloma cells with spleen cells obtained from mice immunized with a pathogenic strain of Pasteurella multocida isolated from a rabbit. Desirable MAbs were selected by enzyme-linked immunosorbent assay, whole-cell radioimmunoprecipitation (WC-RIP), and Western blot (immunoblot) analysis. WC-RIP and Western blot analyses, using MAb 1608 adsorbed with intact P. multocida cells and the eluted MAb, demonstrated that the antigen recognized by this MAb is exposed on the cell surface, is antibody accessible, and has an estimated molecular mass of 37.5 kDa. Treatment of outer membrane vesicles of P. multocida with proteinase K totally abrogated the MAb 1608 activity, indicating that this MAb binds to a protein antigenic determinant. Furthermore, MAb 1608 was nonreactive to purified lipopolysaccharide in Western blot analysis. Passive transfer studies showed that nine rabbits inoculated intranasally with MAb 1608 and homologously challenged intranasally had significantly reduced mortality, severity of pneumonia, prevalence of P. multocida colonization in nonrespiratory organs, and numbers of P. multocida in nasal cavities compared with the controls. Furthermore, the number of P. multocida in lungs was reduced 84,750-fold. Similarly, passive transfer experiments indicated that MAb 1608 protected mice against homologous and heterologous challenges with P. multocida strains bearing the antigenic determinant recognized by MAb 1608. However, no protection was afforded by MAb 1608 when mice were challenged with a P. multocida strain lacking the antigenic determinant recognized by MAb 1608. This study establishes that the 37.5-kDa outer membrane protein is the target for a protective MAb.
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PMID:A monoclonal antibody against a Pasteurella multocida outer membrane protein protects rabbits and mice against pasteurellosis. 198 31

Overall 111 healthy children aged 3 to 7 years, 71 children with ARVI and those aged 2 to 14 years with ARVI complicated by bronchitis and pneumonia were examined. The level and rate of IL-1 production by peripheral blood monocytes in response to lipopolysaccharide (LPS) were determined. It has been established that 98.7% of the healthy children responded to LPS by marked production of IL-1. In 3 children, there was po synthesis of IL-1, in 26.1% of the healthy children, peripheral blood monocytes produced IL-1 without addition of LPS. In children with respiratory bacterial infections, there was a significant increase of IL-1 production as compared to the control. IL-1 production in ARVI was lowered.
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PMID:[Production of interleukin-1 by peripheral blood monocytes in children with respiratory diseases]. 204 81


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