This study will investigate the inflammatory response. People with abnormal regulation of
inflammation and immune defects often have an exaggerated or depressed inflammatory response
that results in poor healing of recurrent infections. This study will measure and compare
amounts of inflammatory mediators (chemicals involved in the inflammatory response) in
healthy normal volunteers and in patients with abnormal immune responses.
Healthy normal volunteers and patients with host defense defects or excessive inflammation,
as in vasculitis syndromes, may be eligible for this study. Patients must be between 6 and 65
years of age.
Participants will have eight small blisters raised on the forearm using a gentle suction
device. The top of the blisters will be removed with scissors and a plastic template will be
placed over the blisters. The wells of the template will be filled with a salt solution or a
mixture of the subject s serum (fluid part of the blood without cells) and a salt solution.
Some blisters may be covered with coverslips a small round piece of very thin sterilized
glass before adding the fluid. Blister fluid will be removed from the wells at 3, 5, 8, and
24 hours with a syringe and analyzed for inflammatory mediators. A scab will form over the
blisters and fall off in about 2 weeks.
Participants will have about 4 tablespoons of blood drawn in order to compare the
inflammatory mediators in the blood with those in the blister fluid.
Patients with abnormal regulation of inflammation and with host defense defects often have an
exaggerated or depressed inflammatory response with resultant difficulty in healing of
recurrent infections. Delayed healing can be manifested by either a delay in wound healing,
granuloma formation along the incision line, or dehiscence of a partially healed wound
without evidence of infection. We are interested in studying the dynamics of host immune
defenses during an experimentally induced inflammatory response using a well-studied suction
blister device. This protocol is designed to study mediators of inflammation in patients with
host defense defects as well as patients with excessive inflammation as in the vasculitis
syndromes. We will measure mediators of inflammation (e.g., C5a, leukotriene B4,
interleukins, chemokines, tumor necrosis factor, interferon-gamma) by ELISA,
radioimmunoassay, High Performance Liquid Chromatography, multiplex cytokine assays, and/or
bioactivity assays. Furthermore, molecular characterization and host defense functions (e.g.,
respiratory burst, chemotaxis, phagocytosis, microbicidal activity) of cells recruited to the
blisters will also be examined. In addition to the analysis of cell function, RNA will be
prepared and subject to DNA microarray or quantitative RT-PCR studies to measure expression
and dynamics of key inflammatory mediators. Many of these factors contribute to the
inflammatory process and several are thought to be important in granuloma formation. If
patients are found to have abnormal amounts of these mediators when compared to healthy
volunteers or patients with other abnormalities it will help us understand the basis for
their disease and new therapeutic strategies. For example, this blister study allowed us to
identify a patient subsequently shown to have IRAK4 deficiency.
- INCLUSION CRITERIA - PATIENTS:
Patients having or thought to have an immune defect between the ages of 6 and 65 years
(inclusive) are eligible to participate.
INCLUSION CRITERIA - NORMAL VOLUNTEERS:
Be a healthy adult of either sex and between the ages of 18 and 65 years old.
Weight greater than 110 pounds.
Not have any heart, lung, or kidney disease, or bleeding disorders.
Not have a history of viral hepatitis (B or C) since age 11.
Not have a history of intravenous injection drug use.
Not have a history of engaging in high-risk activities for exposure to the AIDS virus.
Not be pregnant.
EXCLUSION CRITERIA - PATIENTS:
Patients less than 6 or greater than 65 years of age.
EXCLUSION CRITERIA - NORMAL VOLUNTEER:
Less than 18 years old or older than 65 years.
Have viral hepatitis (B or C).
Receiving chemotherapeutic agent(s), or have underlying malignancy.
Have history of heart, lung, kidney disease, or bleeding disorders.