title: Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.
abstract: Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance.
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, United Kingdom High Ministry of Education Al-Farabi College, Jeddah, Saudi Arabia.
authors.forename: Nawal
authors.initials: N
authors.lastname: Helmi
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, United Kingdom.
authors.forename: Hitesh C
authors.initials: HC
authors.lastname: Pandya
mesh_terms: D061605:Administration, Intravenous; D000755:Anemia, Sickle Cell / Q000150:complications*; D000818:Animals; D058491:Bacterial Load; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004655:Emulsions / Q000627:therapeutic use*; D005466:Fluorocarbons / Q000627:therapeutic use*; D006931:Hyperbaric Oxygenation; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000473:pathology; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D004655:Emulsions; D005466:Fluorocarbons
keywords: Streptococcus pneumoniae; anemia; antisickling agents