Strategies for the treatment of
bacterial pneumonia beyond traditional antimicrobial
therapy have been limited. The recently discovered novel genus of
lipid mediators, coined "specialized proresolving mediators" (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of
inflammation. We performed
lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae
pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae-infected (n = 5-6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with
pneumonia (n = 3), we administered inhaled
carbon monoxide (CO) at 48 hours (200-300 ppm for 60-90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and
lipoxins. In contrast, serum-treated,
zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae
pneumonia produced a proinflammatory LM signature profile with elevated
leukotriene B4 and
prostaglandins. Plasma from baboons with S. pneumoniae
pneumonia also displayed significantly reduced LM-SPM levels, including
eicosapentaenoic acid-derived E-series resolvins (RvE) and
lipoxins. CO inhalation increased levels of plasma RvE and
lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae
pneumonia in baboons and provide evidence for
pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to
pneumonia resolution.