CYCLOSPORINE-A INHIBITS 12-O-TETRADECANOYL-PHORBOL-13-ACETATE-INDUCEDCUTANEOUS INNAMMATION IN SEVERE COMBINED IMMUNODEFICIENT MICE THAT LACK FUNCTIONAL LYMPHOCYTES

A single application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to mouse skin results in an acute inflammatory response, with an influx of neutrophils and lymphocytes, epidermal hyperplasia and abnormal ker atinocyte differentiation. This response is significantly inhibited by topical cyclosporin A (CyA). Although CyA is known to inhibit T-cell activation, the role of T cells in TPA-induced cutaneous inflammation is not well understood. In this study, we have used severe combined im munodeficient (SCID) mice, which carry a spontaneous mutation resultin g in the absence of functional T and B lymphocytes, to examine whether lymphocytes are required for the TPA response in mouse skin and wheth er CyA inhibits the TPA response in SCID mice. A significant increase in epidermal and deep dermal inflammation was observed in both SCID an d CB-17 mice 24 h after a single application of TPA (10 nmol) compared with vehicle (P<0.05, n=5-7). Simultaneous application of CyA (1.7 mu mol) plus TPA resulted in a significant reduction in epidermal and de ep inflammation at 24 h compared with TPA alone in SCID and CB-17 mice (P<0.05, n=7). In contrast to hairless mice, a variable increase in e pidermal thickness was observed in both SCID and CB-17 mice after trea tment with TPA at 24 and 72 h, which was not significantly affected by CyA. These data indicate that TPA-induced inflammation in mouse skin does not depend on lymphocytes. In addition, the inhibition of TPA-ind uced epidermal and deep dermal inflammation by CyA in SCID mouse skin suggests that CyA exerts effects on cutaneous inflammation in mice in the absence of functioning T cells.