Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk and patients affected by cystic fibrosis. However, risk factors for P. aeruginosa infection remain largely unknown. To identify and track the host factors influencing P. aeruginosa lung infections, inbred immunocompetent mouse strains were screened in a pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl, BALB/cByJ, C3H/HeOuJ, C57BL/6J, C57BL/6NCrl, DBA/2J, and 129S2/SvPasCRL mice were infected with P. aeruginosa clinical strain and monitored for body weight and mortality up to seven days. The most deviant survival phenotypes were observed for A/J, 129S2/SvPasCRL and DBA/2J showing high susceptibility while BALB/cAnNCrl and C3H/HeOuJ showing more resistance to P. aeruginosa infection. Next, one of the most susceptible and resistant mouse strains were characterized for their deviant clinical and immunological phenotype by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible A/J mice showed significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, particularly neutrophils, when compared to C3H/HeOuJ resistant mice. Pathologic scores showed lower inflammatory severity, reduced intraluminal and interstitial inflammation extent, bronchial and parenchymal involvement and diminished alveolar damage in the lungs of A/J when compared to C3H/HeOuJ. Our findings indicate that during an early phase of infection a prompt inflammatory response in the airways set the conditions for a non-permissive environment to P. aeruginosa replication and lock the spread to other organs. Host gene(s) may have a role in the reduction of cell-mediated immunity playing a critical role in the control of P. aeruginosa infection. These results now provide a basis for mapping genomic regions underlying host susceptibility to P. aeruginosa infection.
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PMID:Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication. 2526 34

Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (-24 h) or double-dose (-12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (-12 h) combined with oseltamivir at 50 mg/kg (-12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.
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PMID:A broadly neutralizing human monoclonal antibody is effective against H7N9. 2628 46

A theoretical safety concern proposed in the influenza literature is that therapeutic antiviral antibodies could have the potential for antibody-dependent enhancement (ADE) of infection and disease. ADE may occur when virus-specific antibodies at subtherapeutic, nonneutralizing concentrations facilitate virus uptake and, in some cases, enhance replication, which can lead to an exacerbation of virus-mediated disease. Alternatively, ADE may occur due to antibody-dependent complement activation exacerbating virus-mediated disease in the absence of increased replication. As a result of this theoretical safety concern, safety assessment of anti-influenza antibodies may include an in vivo evaluation of ADE of infection and/or disease. These studies were conducted to investigate the potential of MHAB5553A, a broadly specific, neutralizing therapeutic anti-influenza B antibody, to elicit ADE of infection and disease in mouse models of influenza B infection. In parallel studies, female DBA/2J mice were infected with either influenza B/Victoria/504/2000 or influenza B/Brisbane/60/2008 representing distinct lineages. Assessment of ADE was based on an integration of results from multiple endpoints, including infectious lung viral titers and genomes, body weight, mortality, lung weight, and histopathology. In these studies, the high dose of 15 mg/kg MHAB5553A resulted in substantial attenuation of influenza pneumonia, with more modest effects at 1.5 mg/kg; whereas MHAB5553A treatment at 0.15 or 0.015 mg/kg was generally comparable to vehicle-treated controls. Our results demonstrate that MHAB5553A across a broad range of doses did not enhance primary influenza B infection or disease in this model, and represent a nonclinical de-risking of the ADE potential with this antibody.
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PMID:In Vivo Assessment of Antibody-Dependent Enhancement of Influenza B Infection. 3079 34


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