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Article ; Online: Immunotherapy with a combination of intravenous immune globulin and p4 peptide rescues mice from postinfluenza pneumococcal pneumonia.

Weeks, Jenni N / Boyd, Kelli L / Rajam, Gowrisankar / Ades, Edwin W / McCullers, Jonathan A

Antimicrobial agents and chemotherapy

2011  Volume 55, Issue 5, Page(s) 2276–2281

Abstract: ... and intravenous immune globulin. Survival was improved from 20% to 80% in treated mice relative ... The immunomodulatory peptide P4 has shown promise in mouse models of primary pneumococcal infection. Mice infected ... with influenza virus and then challenged with Streptococcus pneumoniae were treated with a combination of P4 peptide ...

Abstract Alternate therapies are needed for treatment of secondary bacterial pneumonia following influenza. The immunomodulatory peptide P4 has shown promise in mouse models of primary pneumococcal infection. Mice infected with influenza virus and then challenged with Streptococcus pneumoniae were treated with a combination of P4 peptide and intravenous immune globulin. Survival was improved from 20% to 80% in treated mice relative to controls. Clinical cure correlated with increased clearance of bacteria and decreased lung consolidation. Greater trafficking of professional phagocytic cells to the site of pneumococcal infection coupled with enhanced opsonophagocytosis as manifest by decreased surface display of Fcγ receptors (FcγR) on neutrophils and macrophages were associated with P4 peptide treatment. This suggests that the mechanism of action for improved clearance of bacteria engendered by P4 is through improved uptake by phagocytes mediated by IgG Fc-Fcγ receptor interactions following antibody-mediated opsonophagocytosis of bacteria. Antibody-based therapies, when coupled with immune modulators, such as P4 peptide, may be an effective tool together with antibiotics in our armamentarium against severe pneumonia.
MeSH term(s) Animals ; Female ; Immunoglobulins, Intravenous/therapeutic use ; Immunotherapy ; Mice ; Mice, Inbred BALB C ; Pneumonia, Pneumococcal/drug therapy ; Pneumonia, Pneumococcal/microbiology ; Streptococcus pneumoniae/drug effects
Chemical Substances Immunoglobulins, Intravenous
Language English
Publishing date 2011-03-07
Publishing country United States
Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID 217602-6
ISSN 1098-6596 ; 0066-4804
ISSN (online) 1098-6596
ISSN 0066-4804
DOI 10.1128/AAC.00057-11
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