title: Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells.
abstract: Therapeutic options for controlling autoimmune diseases are still very limited. Interleukin-10 has been reported to be a promising approach to therapeutic intervention. In the search for a drug which results in the selective upregulation of interleukin-10, we investigated the immunoregulative effects of cordycepin. We have measured interleukin-10 and interleukin-2 secretion of human peripheral blood mononuclear cells that were incubated with cordycepin and assessed the influence of cordycepin on the expression of interleukin-10 mRNA, the proliferative response and the expression of surface markers on T lymphocytes. In addition, the subsets of interleukin-10-secreting cells, the influence of anti-interleukin-10 neutralizing antibody and cytotoxicity of cordycepin were evaluated. Our results suggest that cordycepin has a significantly upregulative effect on interleukin-10 production and interleukin-10 mRNA expression. Interleukin-10-producing cells included in CD4+, CD8+, CD19+, CD56+ and CD14+ cells. At the same time, cordycepin inhibited phytohaemagglutinin-induced interleukin-2 production and proliferation of peripheral blood mononuclear cells. A restricted T lymphocyte activation was also reflected by a reduced expression of the surface markers CD25, CD45RO, CD54, CD71 and HLA DR. Anti-interleukin-10 neutralizing antibody could not completely block the suppressive effect of cordycepin on production of interleukin-2. Cordycepin in the effective concentration presented slight cytotoxicity but did not increase apoptosis. These results indicate that cordycepin exerts immunoregulative effects. Further research on it may provide an approach for the development of novel immunomodulatory drugs which directly alter the secretion of cytokines.
authors.affiliation: Pediatric Immunology and Infectious Diseases, Children's Hospital, Johannes Gutenberg, University of Mainz, Obere Zahlbacher Street 63, D-55131, Mainz, Germany. xzhou@uni-mainz.de
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhou
authors.forename: Claudius U
authors.initials: CU
authors.lastname: Meyer
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidtke
authors.forename: Fred
authors.initials: F
authors.lastname: Zepp
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003839:Deoxyadenosines / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D003839:Deoxyadenosines; D007376:Interleukin-2; D012333:RNA, Messenger; D016753:Interleukin-10; C058120:cordycepin