Epidermal interleukin-8 and its receptor CXCR2 in drug-induced toxic epidermal necrolysis.
BACKGROUND
In drug-induced toxic epidermal necrolysis (TEN), the epidermal destruction is associated with a slight to moderate lymphomonocytic cell infiltrate. Interleukin (IL)-8, which is a keratinocyte-derived pro-inflammatory cytokine, might be involved in this process. The IL-8 receptor CXCR2 has also been shown to be overexpressed in some epidermal disorders.


METHODS
IL-8 concentration was measured by ELISA in both serum and blister fluid from 10 patients with TEN. Data were compared with similar dosages performed in 15 cases of second-degree burn and 7 cases of bullous pemphigoid (BP). CXCR2 expression on keratinocytes was studied using immunohistochemistry on skin biopsies performed in TEN bullous lesions and clinically uninvolved skin of the same patients.


RESULTS
IL-8 was significantly overexpressed in TEN blister fluid compared with TEN serum (P = 0.0015). However, no difference was found in IL-8 concentrations present in blister fluid of TEN, second-degree burn and BP. CXCR2 was moderately expressed in the epidermis of some TEN blisters, but was never expressed in clinically uninvolved skin. CXCR2 expression was not found in the follicular epidermal root sheaths of patients with TEN.


CONCLUSIONS
These results indicate that abundant IL-8 appears to be locally produced in TEN epidermis, but this overexpression is not disease-specific. Because of the paucity of the inflammatory infiltrate in TEN, it is unlikely that IL-8 induces epidermal destruction through its chemotactic activity. Moreover, the complete absence of neutrophils in TEN lesions indicates that the major chemotactic effect of IL-8 on neutrophils is not operative in TEN skin. This implies that IL-8 activates different functions according to the local environment. CXCR2 expression on TEN keratinocytes is expressed on some necrotic keratinocytes, consistent with a discrete IL-8 proapoptotic activity. The lack of CXCR2 expression in the follicular root sheaths argues against a role for IL-8 in TEN epidermal repair.
Paquet
P
P
Department of Dermatopathology, University Hospital of Liège, Belgium. p.paquet@chu.ulg.ac.be
Ribbens
C
C
Piérard
G E
GE
D000328:Adult; D000368:Aged; D001768:Blister / Q000378:metabolism; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D023063:Receptors, Interleukin-8B / Q000097:blood / Q000378:metabolism*; D013262:Stevens-Johnson Syndrome / Q000378:metabolism*
D016209:Interleukin-8; D023063:Receptors, Interleukin-8B