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Alterations induced in normal human skin by in vivo interferon-gamma
J N Barker1, M H Allen, D M MacDonald
1Laboratory of Applied Dermatopathology, United Medical School, Guy's Hospital, London, U.K.
Abstract:
In a study of the direct effects of interferon-gamma (IFN-gamma) on normal human skin, healthy adult male volunteers received either 3 micrograms (n = 4) or 30 micrograms (n = 9) of recombinant IFN-gamma administered intradermally over 3 days. Biopsies were taken on day 6 and histopathological examination of fixed paraffin-embedded sections from sites which had received 30 micrograms IFN-gamma revealed a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells. Immunophenotyping of 5 microns cryostat sections demonstrated that 3 micrograms IFN-gamma induced keratinocyte HLA-DR expression in the absence of any significant infiltrate. More intense keratinocyte HLA-DR expression was produced by 30 micrograms IFN-gamma in all specimens, with HLA-DP concurrently expressed in three biopsies. The ratio of CD4:CD8 cells within the infiltrate was approximately 3:1. CD1 + cells within the epidermis were markedly depleted by 30 micrograms IFN-gamma, while CD1-labelled cells were observed in the dermal perivascular infiltrate. Intradermal IFN-gamma induces similar immunopathological changes to those observed in many of the inflammatory dermatoses.
Insights
Intradermal interferon-gamma (IFN-gamma) in humans causes skin inflammation. This study shows IFN-gamma induces immune cell infiltration and alters keratinocyte marker expression, mimicking inflammatory skin diseases.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Interferon-gamma (IFN-gamma) is a cytokine with diverse immune functions.
- Its direct effects on normal human skin are not fully understood.
- Investigating IFN-gamma's role in skin inflammation is crucial for understanding dermatological conditions.
Purpose of the Study:
- To investigate the direct effects of intradermal recombinant interferon-gamma on normal human skin.
- To characterize the resulting histopathological and immunophenotypic changes.
- To compare these changes to those seen in inflammatory dermatoses.
Main Methods:
- Healthy adult males received intradermal injections of 3 or 30 micrograms of recombinant IFN-gamma over 3 days.
- Skin biopsies were collected on day 6 for histopathological examination.
- Immunophenotyping was performed on cryostat sections to analyze cell populations and marker expression (HLA-DR, HLA-DP, CD1, CD4, CD8).
Main Results:
- 30 micrograms of IFN-gamma induced a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells.
- IFN-gamma stimulated keratinocyte HLA-DR expression, with more intense expression at higher doses.
- CD1+ cells in the epidermis were depleted, while CD1-labelled cells appeared in the dermal infiltrate; CD4:CD8 ratio was approximately 3:1.
Conclusions:
- Intradermal IFN-gamma administration induces significant immunopathological changes in normal human skin.
- These induced changes, including immune cell infiltration and altered keratinocyte marker expression, resemble those observed in various inflammatory dermatoses.
- IFN-gamma may play a direct role in the pathogenesis of inflammatory skin conditions.