Immunotherapy with a combination of intravenous immune globulin and P4 peptide rescues mice from postinfluenza pneumococcal pneumonia

Jenni N. Weeks, Kelli L. Boyd, Gowrisankar Rajam, Edwin W. Ades, Jonathan Mccullers

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10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2276-2281
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number5
DOIs
StatePublished - May 1 2011

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Pneumococcal Pneumonia
Intravenous Immunoglobulins
Immunotherapy
Pneumococcal Infections
Fc Receptors
Phagocytes
Bacteria
Bacterial Pneumonia
Antibodies
Therapeutics
Streptococcus pneumoniae
Orthomyxoviridae
Human Influenza
Pneumonia
Neutrophils
Immunoglobulin G
Macrophages
Anti-Bacterial Agents
Lung
peptide P4

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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.

In: Antimicrobial Agents and Chemotherapy, Vol. 55, No. 5, 01.05.2011, p. 2276-2281.

Research output: Contribution to journalArticle

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