Intratracheal instillation of PMN rescues bacterial overgrowth initiated by trauma DAMPs.

Background: Nosocomial pneumonias are common in trauma patients and so interventions to prevent and treat nosocomial pneumonia may improve outcomes. Our prior work strongly suggests that tissue injury predisposes to infections like nosocomial pneumonia because mitochondrial debris (MTD) originating from injured cells contains damage-associated molecular patterns (DAMPs) that can reduce neutrophil (PMN) migration into the airway and diminish PMN function in response to bacterial inoculation of the airway. This suggested that putting exogenous "normal" PMN into the airway might be beneficial. Methods: Post-injury pneumonia (PNA) commonly arises in two groups, early, community-acquired PNA (CAP) and later hospital-acquired PNA (HAP). Post-traumatic Early onset CAP and Late onset HAP were modeled in CD-1 mice using S. aureus (SA) or P. aeruginosa (PA) instilled intra-tracheal (i.t.) at clinically relevant times with or without extrapulmonary injuries mimicked by an intraperitoneal application of mitochondrial DAMPs. We applied bone-marrow derived PMN intratracheally to access bacterial clearance in the lung. Results: BM-PMN instillation i.t. had no untoward clinical effects on recipient animals. In both the Early/CAP and Late/HAP models, clearance of the inoculum from the lung was suppressed by MTD and restored to uninjured levels by i.t. instillation of exogenous BM-PMN. PMN instillation was capable of clearing P. aeruginosa that could not cleared by uninjured mice. The instillation of PMN into the lung, even across strains (CD-1 vs. C57BL/6) had no injurious effect. Conclusion: These initial studies suggest PMN instillation (i.t.) is worthy of further study as a potential adjunctive therapy aimed at decreasing the morbidity of lung infections in trauma patients. Moreover, PMN instillation (i.t.) may represent a unique means of preventing or treating pneumonia after serious injury that is completely independent of the need for antibiotic use. Level of evidence: Pre-clinical therapeutic study, level II. (C) 2017 Lippincott Williams & Wilkins, Inc.

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