Bacterial infections can progress to a life-threatening illness called septic shock,
characterized by low blood pressure and vital organ damage. The syndrome is thought to be
caused by parts of the bacteria and by the body s own immune response to the infection. A
major bacterial product that interacts with the immune defenses is called endotoxin. This
study will examine the body s response to endotoxin in the lungs or bloodstream. When
endotoxin is given in small amounts to humans, even though it is not an infection, it
triggers a set of responses that are typical of what one would see with a true bacterial
infection. This allows us to study the earliest changes in molecules and cells that are
involved in some bacterial infections. This type of model is safe and has been used in humans
for many years to understand the body s responses during infections.
Normal volunteers 18 to 45 years of age may be eligible for this study. Candidates will have
a history and physical examination, blood and urine tests, electrocardiogram (EKG) and chest
X-ray. In addition, volunteers 40 to 45 years old will have an exercise stress test to screen
for asymptomatic coronary artery disease. Participants will undergo one or more of the
following procedures:
Bronchoscopy, Bronchoalveolar Lavage, Bronchial Brushings, and Endobronchial Mucosal
Biopsies: These techniques for examining lung function are used routinely in patient care and
clinical research. The mouth and nasal and lung airways are numbed with an anesthetic. A
bronchoscope (pencil-thin flexible tube) is then passed through the nose into the large
airways of the lung. Cells and secretions from the airways are rinsed with salt water
(bronchoalveolar lavage) and a flexible brush the size of a pencil tip is passed through the
bronchoscope to scrape cells lining the airways. Lastly, pieces of tissue (the size of the
ball of a ballpoint pen) lining the airways are removed for examination under the microscope.
Intravenous Endotoxin: A small dose of endotoxin is injected into a vein. Blood samples are
drawn at regular intervals for 8 hours after the injection and again after 1, 2, 3, 7 and 14
days to analyze the body s immune response to the bacteria in the blood.
Instilled Endotoxin in the Lungs: A small amount (2 teaspoons) of salt water is squirted
through a bronchoscope into a lobe of one lung, and then salt water containing a small dose
of endotoxin is squirted into the other lung. Bronchial lavage, brushing, and biopsy (see
above) are then done to study the response of the lung to the endotoxin. In addition, air is
withdrawn through the bronchoscope to study air components from the lung that was instilled
with salt water or endotoxin.
Nitric Oxide Therapy: Endotoxin is instilled in a lung (see above) and then nitric oxide a
colorless, odorless, tasteless gas mixed with room air in a concentration of 40 parts per
million, is given through a cushioned mask placed over the mouth and nose. (Some participants
will be given the nitric oxide mixture and others will breathe only room air through the mask
to test the effects of the nitric oxide on the lung inflammation.) The mask will be worn
continuously for 6 hours and removed before repeat bronchoscopy with lavage, brushing and
biopsy.
Some of the above procedures require placement of a catheter (thin plastic tube) in a wrist
artery to monitor blood pressure from heartbeat to heartbeat and to collect blood samples.
First, the skin is numbed with an anesthetic (lidocaine). A needle is then inserted into the
artery, the catheter is slipped over the needle into the vessel, and the needle is removed.
Phase:
Phase 1
Details
Lead Sponsor:
National Institutes of Health Clinical Center (CC)