Bavandi, Assadollah, Fahrngruber, Hermann, Aschauer, Heinrich, Hartmann, Boris, Meingassner, Josef and Kalthoff, Frank (2006) Pimecrolimus and tacrolimus differ in their inhibition of lymphocyte activation during the sensitization phase of contact hypersensitivity. Journal of Dermatological Science, 43 (2). pp. 117-126. ISSN 0923-1811

Abstract

BACKGROUND: As reported previously, oral administration of the calcineurin inhibitors (CNI) pimecrolimus and tacrolimus resulted in equipotent inhibition of the elicitation phase of contact hypersensitivity (CHS) in mice. The sensitization phase was inhibited by tacrolimus but was unaffected by pimecrolimus, even at higher doses. OBJECTIVE: The kinetics of lymph node hyperplasia and up-regulation of T and B cell activation antigens were analyzed to obtain a better understanding of the divergent CNI profile in CHS.
METHODS: Lymph node (LN) cells of CNI-untreated and treated mice were examined with flow cytometry at various time points after sensitization with oxazolone. LN hyperplasia and drug levels were also determined.
RESULTS: Sensitization induced a higher portion of LN cells expressing the activation antigens CD25, CD69 and CD134 and an increase in activated B cells (B220(+)/CD40(+)) compared to naïve mice. Up-regulation of these markers was completely or profoundly blocked with tacrolimus, whereas pimecrolimus at the three-fold higher dose caused significantly less inhibition. Tacrolimus also completely blocked the sensitization-associated increase of CD11c(+) antigen presenting cells (APC) in LN, whereas pimecrolimus showed significantly less inhibition. In contrast to tacrolimus, LN weight and cellularity were not affected by pimecrolimus at any time point after sensitization. Concentration of tacrolimus in blood and in the draining LN substantially exceeded that of pimecrolimus by factors 6.7-14 and 5.6-5.8, respectively, at the same dose levels.
CONCLUSION: In contrast to tacrolimus, systemic treatment of mice with pimecrolimus only weakly interferes with lymphocyte activation and does not affect hyperplasia of the draining lymph nodes during sensitization.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jdermsci.2006.04.001
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Pimecrolimus; Tacrolimus; Lymphocyte activation; Lymph node hyperplasia; Sensitization phase; Contact hypersensitivity; Drug levels
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.jdermsci.2006.04.001
Date Deposited:	14 Dec 2009 14:00
Last Modified:	31 Jan 2013 01:18
URI:	https://oak.novartis.com/id/eprint/399