National Institutes of Health Clinical Center (CC)
Background: \- When bacteria enter the lungs, serious infections can occur. Researchers want to learn more about the process of inflammation in the lungs by studying lung cells and the products that they make. Lung cells are influenced by infections, smoking, and molecules made within the body. Researchers also want to learn more about one of these molecules, called microRNA (or micro ribonucleic acid). Objective: \- To better how the body responds to infection. Also, to understand which cells in the lung secrete microRNA and how they may influence other lung cells. Eligibility: \- Healthy, non-smoking adults ages 18-45. Design: * Participants will be screened with a medical history and physical exam. They will have blood and urine tests and an electrocardiogram. * Participants will have blood drawn from an arm vein. They will have an intravenous catheter (small plastic tube) placed in a vein. * All participants will have bronchoscopy with bronchoalveolar lavage. They will be numbed with medicine. A thin flexible tube will be placed through the nasal passages or the mouth into the airways of the lung. * Some participants will have bronchoscopy with bronchoalveolar lavage (rinsing the airways with salt water) in order to obtain cells from lung. The water will then be suctioned out. * Some participants will have two bronchoscopies; during the first procedure, endotoxin, a molecule found in bacteria is squirted into a small portion of the lung. Endotoxin is a molecule that acts like an infection but isn t one. After 6 to 48 hours, bronchoscopy with with bronchoalveolar lavage will be done to look at the lung s response to endotoxin. * Participants heart rhythm and rate, temperature and blood oxygen level will be monitored during the procedures. * Participants will be called the next day to see how they are feeling.
Defining the mechanisms that limit tissue injury during acute inflammation may provide the basis for preventing secondary organ dysfunction during serious infections. We plan to use the human endotoxin lung challenge model to study mechanisms associated with the initiation and resolution of lung inflammation. Endotoxin (LPS), an outer membrane component of Gram-negative bacteria, is a major microbial factor that mediates inflammation associated with serious infections. For over fifty years, endotoxin has been administered to humans as a challenge agent in order to understand basic mechanisms…
* INCLUSION CRITERIA: 1. Healthy 18 to 45 year old, nonsmoking subjects based on screening examination and laboratory tests. 2. No significant active medical problems. This would include but not be limited to any cardiac disorder (e.g. arrhythmia, valvular heart disease), pulmonary disease (e.g. asthma requiring chronic medications, chronic bronchitis, emphysema), neurologic disorder (e.g. epilepsy), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder (e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid disease), liver disease (e.g. hepatitis), ga…
Investigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6 hours after 1800 of normal Saline installed in six 30 mL aliquots into the left (lingual) and right (middle lobe) lung segments (360 mL total).
Investigate the changes in miRNA signatures found in BAL and lung cells from healthy volunteers at baseline and at 6, 24, or 48 hours after endotoxin segmental lung challenge.