ABSTRACT
Pneumonia caused by the intracellular bacterium Rhodococcus equi is an important cause of disease and death in immunocompromised hosts, especially foals. Antibiotics are the standard of care for treating R. equi pneumonia in foals, and adjunctive therapies are needed. We tested whether nebulization with TLR agonists (PUL-042) in foals would improve innate immunity and reduce the severity and duration of pneumonia following R. equi infection. Neonatal foals (n = 48) were nebulized with either PUL-042 or vehicle, and their lung cells infected ex vivo. PUL-042 increased inflammatory cytokines in BAL fluid and alveolar macrophages after ex vivo infection with R. equi. Then, the in vivo effects of PUL-042 on clinical signs of pneumonia were examined in 22 additional foals after intrabronchial challenge with R. equi. Foals infected and nebulized with PUL-042 or vehicle alone had a shorter duration of clinical signs of pneumonia and smaller pulmonary lesions when compared to non-nebulized foals. Our results demonstrate that host-directed therapy can enhance neonatal immune responses against respiratory pathogens and reduce the duration and severity of R. equi pneumonia.
Subject(s)
Actinomycetales Infections , Horse Diseases , Horses , Immunity, Innate/drug effects , Lipopeptides/pharmacology , Oligodeoxyribonucleotides/pharmacology , Pneumonia, Bacterial , Rhodococcus equi/immunology , Toll-Like Receptor 2/agonists , Toll-Like Receptor 6/agonists , Toll-Like Receptor 9/agonists , Actinomycetales Infections/drug therapy , Actinomycetales Infections/immunology , Actinomycetales Infections/pathology , Actinomycetales Infections/veterinary , Animals , Horse Diseases/drug therapy , Horse Diseases/immunology , Horse Diseases/pathology , Horses/immunology , Horses/microbiology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/pathology , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/veterinary , Severity of Illness IndexABSTRACT
OBJECTIVE: To evaluate the outcome in horses treated with a rolling technique or surgically for nephrosplenic entrapment of the large colon (NSE) and to examine the benefit of phenylephrine (PE) HCl on the efficacy of nonsurgical (rolling) management of NSE. STUDY DESIGN: Case series. ANIMALS: Horses (n = 211) diagnosed with NSE by rectal palpation with or without ultrasonography, or at the time of exploratory celiotomy or necropsy. METHODS: Medical records (January 1, 2001-September 1, 2008) were collected from horses diagnosed with NSE at 2 referral centers. Records were used to obtain signalment, physical exam findings, laboratory results, ultrasonographic findings, the use of PE HCl, the specific treatment used, and outcome. Rectal findings indicative of NSE were: (1) palpation of large colon within the nephrosplenic space or (2) palpation of colonic bands coursing dorsally toward the nephrosplenic space in association with ultrasonographic findings suggestive of NSE. RESULTS: Rolling was successful in 50 of 87 (58%) horses, 85 horses (98%) survived to discharge. Horses (n = 155) that were treated surgically (42 of which had previously undergone the rolling procedure) had a 94% short-term survival rate. Premedication with PE resulted in no significant difference (P = .91) in resolution of NSE by rolling. CONCLUSIONS: Resolution of NSE by rolling was not significantly affected by premedication with PE in the population studied.
