Site-specific suppression of cell-mediated immunity by cyclosporine.
In this study, it was demonstrated that site-specific suppression of T-cell-mediated immune responsiveness could indeed be achieved by topical application of cyclosporine. Evidence for site-specific immune suppression was obtained from a dual skin allograft model in rats. These animals were given an initial 10-d systemic treatment of CsA. Subsequently, one allograft was treated with topical CsA and the other was treated with the vehicle alone. Anti-inflammatory efficacy and prolonged skin allograft survival were observed both grossly and histopathologically in the presence of topically administered CsA, while contralateral vehicle-treated control grafts underwent vigorous rejection. Systemic lymphocyte DNA synthesis following Con-A and PHA stimulation was normal to elevated. Therefore, systemic T-cell-mediated immunity appeared unaffected or possibly activated even with concomitant topical CsA treatment. CsA levels were low systemically, and showed relative site-specificity in terms of tissue concentration. In conclusion, this study indicates that topical CsA is capable of locally suppressing a strong T-cell-mediated immune response after an initial short-term systemic dose of CsA. Furthermore, certain putative autoimmune and inflammatory diseases of the skin, such as psoriasis and eczematous dermatitis, which may share common mechanisms of action compared to skin allograft rejection should likewise benefit from topical CsA treatment.
Black
K S
KS
Transplantation Laboratory, University of California, Irvine 92717.
Nguyen
D K
DK
Proctor
C M
CM
Patel
M P
MP
Hewitt
C W
CW
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D006084:Graft Rejection; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology
D003524:Cyclosporins