Research in Skin Inflammation
Research in Skin Inflammation
This study will examine the production of proteins called chemokines in inflammatory skin
 reactions. It is thought that chemokines attract or recruit white blood cells from the blood
 stream into the skin when there is a skin injury or infection, causing inflammation. This
 study will examine chemokine production in induced inflammatory reactions to try to gain a
 better understanding of how white blood cells are attracted to inflamed areas of the body.

 Healthy normal volunteers between 33 and 60 years old may be eligible for this study if they
 1) have no history of chronic skin disease; 2) are not allergic to eggs; and 3) do not tend
 to form large irregular scars after trauma to the skin from, for example, cuts, scratches and
 surgical incisions. Candidates will be asked a short series of questions and have a limited
 skin examination.

 Participants will have 10 ml (2 tablespoons) of blood drawn from an arm vein at the start and
 end of the 5-day study and undergo the following procedures:

 1. Day 1 - Participants receive an injection in the right upper arm of mumps antigen (a
 protein commonly used to tests for immunization against mumps) and an injection of
 "vehicle" (saline plus the preservatives thimerosal, glycine and formaldehyde) in the
 left upper arm.

 2. Day 3 - Participants who develop a swelling from the mumps antigen larger than 5 mm wide
 will receive another injection of antigen in the right arm and another injection of
 vehicle in the left arm. Those whose swelling is not greater than 5 mm will be excluded
 from the study at this point.

 3. Day 5 - All four injection sites, plus another site on the left upper arm will be
 biopsied. For this procedure the five injection areas are numbed with a local
 anesthetic. A punch biopsy instrument that resembles a small cookie cutter (about
 one-third the diameter of a dime) is inserted about one-fifth of an inch deep into the
 skin and the tissue is removed. Two stitches are used to close the wound. Antibiotic and
 bandages are applied for 5 days. Nine days after the biopsy the participant returns to
 NIH for removal of the stitches.

 New molecular biology techniques will be used to measure changes in chemokine production in
 the biopsied tissue.
In the skin, T lymphocytes are critical modulators and effectors of acquired defense
 responses such as delayed-type hypersensitivity (DTH). T lymphocytes and other leukocytes are
 recruited to the challenged site via the interaction of selectins, integrins, immunoglobulin
 gene superfamily molecules with their ligands, and cytokines including the large and growing
 chemokine group. Endogenous proinflammatory agents such as Tumor Necrosis Factor (TNF)-alpha
 and Interleukin-1 (IL-1) modulate lymphocyte recruitment via up-regulation of endothelial
 adhesion molecules and chemokines. In vitro evidence suggests that endothelial cell-derived
 chemokines may play a crucial role in inducing firm arrest of leukocytes on endothelial cells
 prior to transmigration. However, the investigation of the expression patterns and regulation
 of chemokines in human skin has been limited. Our goal is to qualitatively and quantitatively
 investigate changes in chemokine expression patterns in human skin using a DTH response to
 mumps antigen as a model T cell mediated immunological response. We will study the effects of
 intradermal injection of mumps antigen on cutaneous chemokine expression in healthy human
 volunteers over a five-day period. Skin biopsies of treated and mock-treated areas will be
 obtained and processed for state-of-the-art, real-time quantitative RT-PCR analysis of mRNA
 for chemokines and related molecules of interest. Routine and immunohistological analysis of
 chemokine receptor, chemokines, cytokines and other cell markers on fixed and frozen tissue
 will also be performed in an attempt to correlate chemokine expression patterns with the
 influx of leukocyte subsets into skin. Our hypothesis is that the chemokines will be
 up-regulated, but that the kinetics and expression patterns of individual chemokines may not
 be identical, thus possibly accounting for the differential recruitment of T lymphocytes and
 other leukocytes during the course of the DTH response. Chemokine expression as determined by
 quantitative RT-PCR will be compared with results obtained semi-quantitatively by
 immunohistochemical staining. This study may increase the understanding of the pathogenic
 mechanisms of inflammatory diseases that are characterized by the recruitment of T
 lymphocytes, thus possibly identifying targets for the treatment of cutaneous inflammatory
 diseases such as psoriasis.
Male or Female

 Age: 33-60 years.

 No ingestion of aspirin, ibuprofen, corticosteroids, COX-2 inhibitor such as Rofecoxib, or
 other non-steroidal anti-inflammatory agents within 7 days of start of protocol.

 No history of psoriasis or other chronic skin disease.

 No known underlying chronic disease for which volunteer takes systemic medications.

 Immunocompromised individuals are not eligible.

 Patients with an allergy to eggs and/or thimerosal are not eligible.

 Individuals with a history or physical evidence of keloid or hypertrophic scarring
 resulting from skin trauma are not eligible.

 Patients with a history of HIV, HTLV-1, or other immunodeficiency syndrome are not
 eligible.