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Phage therapy of pneumonia and inflammatory response

 

Nicolas Dufour, Raphaëlle Delattre, Anne Chevallereau, Jean-Damien Ricard, Laurent Debarbieux

Phage therapy of pneumonia is not associated with an over stimulation of the inflammatory response compared to antibiotic treatment in mice

Antimicrobial Agents and Chemotherapy, Jun 2019, AAC.00379-19. DOI: 10.1128/AAC.00379-19

ABSTRACT
Background. Supported by years of clinical use in some countries and more recently by literature on experimental models as well as compassionate use in Europe and in USA, bacteriophage (phage) therapy is providing a solution for difficult to treat bacterial infections. However, studies of the impact of such treatments on the host remain scarce.

Methods. Murine acute pneumonia initiated by intranasal instillation of two pathogenic strains of Escherichia coli (536 and LM33) were treated by two specific bacteriophages (536_P1 and LM33_P1; intranasal) or antibiotics (Ceftriaxone, Cefoxitin, Imipenem-Cilastatin; intraperitoneal). Healthy mice also received phages alone. Severity of pulmonary edema, acute inflammatory cytokines (blood and lung homogenates), complete blood count, bacteria and bacteriophages counts were obtained at early (≤12h) and late (≥20h) time points.

Results. Bacteriophage's efficacy to decrease bacterial load was faster than antibiotics, but both displayed similar endpoints. Bacteriophage treatment was not associated with an over-inflammation but in contrast tended to lower inflammation and provided a faster correction of blood cell count abnormalities compared to antibiotics. In absence of bacterial infection, bacteriophage 536_P1 promoted a weak increase in the production of anti-viral cytokines (INF-γ and IL-12) and chemokines in the lungs, but not in the blood. However, such variations were no longer observed when bacteriophage 536_P1 was administered to treat infected animals.

Conclusions. The rapid lysis of bacteria by bacteriophages in vivo does not increase the innate inflammatory response compared to antibiotic treatment.