Document Detail

The T-cell suppressive effect of bufadienolides: structural requirements for their immunoregulatory activity.
MedLine Citation:
PMID:  11367509     Owner:  NLM     Status:  MEDLINE    
Many studies indicate that substances similar to cardenolides and bufadienolides naturally occur in mammals. The majority of previous studies focused on their cardiovascular, renal, and central nervous action. We analyzed the immunoregulatory property of 52 bufadienolides. Human T-cells were stimulated "in vitro" with mitogens or alloantigens in the presence of bufadienolides. The most active compound totally inhibited T-cell activity at a concentration of 0.75 pmol/10(5) cells. This effect is 16,384 x stronger than that of cortisol and 256 x stronger than that of cyclosporin A or tacrolimus. Preactivated T cells were downregulated and, most importantly, suppressed viable T cells could not be restimulated. Lack of the 17 beta-lactone ring dramatically reduced the activity of bufadienolides. Substitution at C3 also affected their function: components with a 3-OH group were up to 1000 x stronger than those without. The replacement of 14 beta-OH with an epoxy-group slightly decreased the activity. Because there is evidence that the latter change abolishes the cardiac activity, this finding is relevant for therapeutic applications in which immunosuppression without the risk of cardiotoxicity is attempted. One of the substances analyzed in this study was Proscillaridin A. A similar bufadienolide occurs naturally in mammals. We speculate that bufadienolides represent an important bioregulatory link between the cardiovascular, nervous and immune systems.
P Terness; D Navolan; C Dufter; B Kopp; G Opelz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International immunopharmacology     Volume:  1     ISSN:  1567-5769     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-05-22     Completed Date:  2001-06-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  119-34     Citation Subset:  IM    
Institute of Immunology, Department of Transplantation Immunology, INF 305, University of Heidelberg, 69120 Heidelberg, Germany.
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MeSH Terms
Bufanolides / chemistry*,  pharmacology*
Cell Survival / drug effects
Concanavalin A / pharmacology
Drug Evaluation, Preclinical
Immunosuppressive Agents / immunology*,  pharmacology*
Isoantigens / administration & dosage
Lymphocyte Activation / drug effects
Mitogens / pharmacology
Phytohemagglutinins / pharmacology
Proscillaridin / chemistry,  pharmacology
Structure-Activity Relationship
T-Lymphocytes / cytology,  drug effects*,  immunology*
Reg. No./Substance:
0/Bufanolides; 0/Immunosuppressive Agents; 0/Isoantigens; 0/Mitogens; 0/Phytohemagglutinins; 11028-71-0/Concanavalin A; 466-06-8/Proscillaridin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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