Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is a rare drug-induced disease for which t he pathomechanism remains poorly understood. The effector cells of epiderma l injury in TEN were studied by taking skin biopsies of early lesions in 23 TEN patients and by performing immunohistochemical tests using antibodies to factor XIIIa (type I dendrocytes), L1-protein (mainly Mac 387(+) monocyt es and macrophages), UCLH1 (mainly CD45R0(+) T-memory lymphocytes), interle ukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha). Computerized im age analysis was used to evaluate the cell density relative to each immunol abeling. A statistical analysis of cellular counts revealed a numeric relat ion between the cell types in skin with TEN. Factor XIIIa(+) dendrocytes we re abundant and plump in the dermis, although Mac 387(+) macrophages were t he most numerous inflammatory cells in the epidermis. Their numbers greatly exceeded those of CD45R0(+) T lymphocytes and cells showing immunoreactivi ty for either IL-6 or TNF alpha. In the epidermis, IL-6(+) cells were signi ficantly less numerous than TNF alpha(+) cells. No quantitative difference was found between IL-6(+) and CD45R0(+) cell populations. Correlations were observed between either the numbers of TNF alpha(+) cells or Mac 387(+) ma crophages and CD45R0(+) lymphocytes. In the dermis, a significant correlati on was also present between the numbers of Mac 387(+) and factor XIIIa(+) c ells. These findings highlight the complex interactions between the inflamm atory cells that mediate epidermal damage in skin with TEN. The high densit y of factor XIIIa(+) dendrocytes and Mac 387+ macrophages in lesional skin assigns these cellular populations a prominent role in the pathomechanism o f TEN. Despite a lower cell density, CD45R0(+) T-memory lymphocytes likely participate in TNF alpha- and IL-6-regulated processes in the epidermis of TEN. TNF alpha seems to be a major cytokine involved in TEN, although a les s prominent role can be ascribed to IL-6.