In situ localization of chloroquine and immunohistological studies in UVB-irradiated skin of photosensitive patients.
Chloroquine can prevent photosensitivity reactions, but its mechanism of action is poorly understood. To investigate if the drug may interfere with inflammatory or immunological mechanisms of the UV-induced erythema of photosensitive patients, we studied the localization of chloroquine in the skin and its effect on the epidermal/dermal expression of IL-1, TNF-alpha, IL-6 and ICAM-1 and the occurrence of different lymphoid cells in normal skin and UVB-induced erythema in 8 patients with photosensitive discoid and systemic lupus erythematosus and 4 patients with polymorphic light eruption (PMLE), before and during chloroquine treatment. Using a specific monoclonal antibody against chloroquine, we found a strong granular staining pattern of mainly keratinocytes in all biopsy specimens from normal and erythematous skin during chloroquine treatment. In non-irradiated skin, T lymphocytes, macrophages and HLA-DR expressing cells were sparsely distributed within the dermis in similar amounts before and during chloroquine treatment. In UVB-induced erythema an increase in the number of these cells, mainly located in the dermal perivascular area, was seen before medication. During chloroquine treatment such cellular infiltration was reduced. ICAM-1 expression was detected on the endothelium of dermal vessels but not on keratinocytes. The accumulation of chloroquine in the epidermis and the decreased cellular infiltration in erythematous skin during chloroquine treatment indicate a local anti-inflammatory effect. This effect may be due to either unspecific UV-protective properties of the drug or to some specific downregulating action by chloroquine on keratinocyte function.
Sjölin-Forsberg
G
G
Department of Dermatology, University Hospital, Uppsala, Sweden.
Berne
B
B
Eggelte
T A
TA
Karlsson-Parra
A
A
D000293:Adolescent; D000328:Adult; D002738:Chloroquine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism; D004890:Erythema / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008179:Lupus Erythematosus, Discoid / Q000188:drug therapy / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000188:drug therapy / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D006684:HLA-DR Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002738:Chloroquine