Juan Muñoz-Miralles1,2, Bruno C Trindade3, Pablo Castro-Córdova1,2, Ingrid L Bergin4, Leslie A Kirk4, Fernando Gil1,2, David M Aronoff5, Daniel Paredes-Sabja1,2. 1. Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile. 2. Microbiota-Host Interactions & Clostridia Research Group, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile. 3. Department of Pathology, The University of Massachusetts Medical School, Worcester, 01605 MA, USA. 4. The Unit for Laboratory Animal Medicine, The University of Michigan, Ann Arbor, 48109 MI, USA. 5. Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, 37232 TN, USA.
Abstract
AIM: To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficile infection (CDI) severity. MATERIALS & METHODS: Indomethacin was administered in two different mouse models of antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin. RESULTS: Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1β and IL-22 compared with infected mice unexposed to indomethacin. CONCLUSION: These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.
AIM: To evaluate the effect on the nonsteroidal anti-inflammatory drug indomethacin on Clostridium difficileinfection (CDI) severity. MATERIALS & METHODS:Indomethacin was administered in two different mouse models of antibiotic-associated CDI in two different facilities, using a low and high dose of indomethacin. RESULTS:Indomethacin administration caused weight loss, increased the signs of severe infection and worsened histopathological damage, leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed mice infected with C. difficile had enhanced intestinal inflammation with increased expression of KC, IL-1β and IL-22 compared with infected mice unexposed to indomethacin. CONCLUSION: These results demonstrate a negative impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in mice and suggest that targeting the synthesis or signaling of prostaglandins might be an approach to ameliorating the severity of CDI.
Entities:
Keywords:
C. difficile infection severity; NSAID; antibiotic-associated CDI; indomethacin; prostaglandins
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