tetano
Editor, Senior Moderator
Front Immunol. 2019 Aug 14;10:1864. doi: 10.3389/fimmu.2019.01864. eCollection 2019.
[h=1]In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection.[/h] Sharma-Chawla N[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Stegemann-Koniszewski S[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Christen H[SUP]2[/SUP], Boehme JD[SUP]2,[/SUP][SUP]3[/SUP], Kershaw O[SUP]5[/SUP], Schreiber J[SUP]4[/SUP], Guzm?n CA[SUP]6,[/SUP][SUP]7[/SUP], Bruder D[SUP]2,[/SUP][SUP]3[/SUP], Hernandez-Vargas EA[SUP]1[/SUP].
[h=3]Author information[/h] 1 Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany. 2 Immune Regulation Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. 3 Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Health Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 4 Experimental Pneumology, University Hospital of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 5 Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany. 6 Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. 7 Centre for Individualized Infection Medicine (CiiM), Hanover, Germany.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] IFN-γ neutralization; IL-6 neutralization; Influenza Virus; Streptococcus pneumoniae; co-infection; mathematical modeling
PMID: 31474978 PMCID: PMC6702285 DOI: 10.3389/fimmu.2019.01864
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[h=1]In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection.[/h] Sharma-Chawla N[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Stegemann-Koniszewski S[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Christen H[SUP]2[/SUP], Boehme JD[SUP]2,[/SUP][SUP]3[/SUP], Kershaw O[SUP]5[/SUP], Schreiber J[SUP]4[/SUP], Guzm?n CA[SUP]6,[/SUP][SUP]7[/SUP], Bruder D[SUP]2,[/SUP][SUP]3[/SUP], Hernandez-Vargas EA[SUP]1[/SUP].
[h=3]Author information[/h] 1 Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany. 2 Immune Regulation Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. 3 Infection Immunology Group, Institute of Medical Microbiology, Infection Prevention and Control, Health Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 4 Experimental Pneumology, University Hospital of Pneumology, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 5 Department of Veterinary Medicine, Institute of Veterinary Pathology, Free University Berlin, Berlin, Germany. 6 Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. 7 Centre for Individualized Infection Medicine (CiiM), Hanover, Germany.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] IFN-γ neutralization; IL-6 neutralization; Influenza Virus; Streptococcus pneumoniae; co-infection; mathematical modeling
PMID: 31474978 PMCID: PMC6702285 DOI: 10.3389/fimmu.2019.01864
Free full text