In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection.

Abstract

An overt pro-inflammatory immune response is a key factor contributing to lethal pneumococcal infection in an influenza pre-infected host and represents a potential target for therapeutic intervention. However, there is a paucity of knowledge about the level of contribution of individual cytokines. Based on the predictions of our previous mathematical modeling approach, the potential benefit of IFN-γ- and/or IL-6-specific antibody-mediated cytokine neutralization was explored in C57BL/6 mice infected with the influenza A/PR/8/34 strain, which were subsequently infected with the Streptococcus pneumoniae strain TIGR4 on day 7 post influenza. While single IL-6 neutralization had no effect on respiratory bacterial clearance, single IFN-γ neutralization enhanced local bacterial clearance in the lungs. Concomitant neutralization of IFN-γ and IL-6 significantly reduced the degree of pneumonia as well as bacteremia compared to the control group, indicating a positive effect for the host during secondary bacterial infection. The results of our model-driven experimental study reveal that the predicted therapeutic value of IFN-γ and IL-6 neutralization in secondary pneumococcal infection following influenza infection is tightly dependent on the experimental protocol while at the same time paving the way toward the development of effective immune therapies.

• Authors: Niharika Sharma-Chawla, Sabine Stegemann-Koniszewski, Henrike Christen, Julia D Boehme, Olivia Kershaw, Jens Schreiber, Carlos A Guzmán, Dunja Bruder, Esteban A Hernandez-Vargas
• Journal: Frontiers in immunology (Front Immunol) Vol. 10 Pg. 1864 ( 2019) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 31474978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Cytokines
• Interleukin-6
• Interferon-gamma

Topics

• Algorithms
• Animals
• Antibodies, Neutralizing (immunology)
• Coinfection (immunology, microbiology, virology)
• Cytokines (immunology, metabolism)
• Female
• Humans
• Influenza A virus (immunology, physiology)
• Interferon-gamma (immunology, metabolism)
• Interleukin-6 (immunology, metabolism)
• Lung (immunology, microbiology, virology)
• Mice, Inbred C57BL
• Models, Immunological
• Neutralization Tests
• Orthomyxoviridae Infections (immunology, virology)
• Pneumococcal Infections (immunology, microbiology)
• Pneumonia (immunology, microbiology, virology)
• Streptococcus pneumoniae (immunology, physiology)