Minocycline inhibits antigen processing for presentation to human T cells: additive inhibition with chloroquine at therapeutic concentrations.
The ability of minocycline to inhibit processing of tetanus toxoid (TT) for presentation to human T cells was tested. Peripheral blood antigen presenting cells (APC) were incubated with TT before or after addition of test compounds for 4 h. APC were then fixed with paraformaldehyde, and added to autologous TT-responsive T cell lines for a proliferation assay. Minocycline (0.1-0.4 mM) gave significant inhibition of T cell response to TT and was equivalent to chloroquine. Inhibition was not observed when TT was incubated with APC before minocycline, indicating that presentation of preprocessed antigen was not inhibited. Minocycline, doxycycline, and tetracycline all inhibited the proliferation of PBMC to TT. The combination of minocycline and chloroquine resulted in additive inhibition at clinically relevant levels of both drugs (3.7 microM). This study suggests a novel immunosuppressive mechanism for minocycline, as well as possible additive anti-inflammatory effect when combined with chloroquine or hydroxychloroquine.
Kalish
Richard S
RS
Department of Dermatology, State University of New York at Stony Brook, Stony Brook, NY 11794-8165, USA. richard.kalish@stonybrook.edu
Koujak
Susan
S
D017951:Antigen Presentation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D008911:Minocycline / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D013745:Tetanus Toxoid / Q000494:pharmacology
D013745:Tetanus Toxoid; D002738:Chloroquine; D008911:Minocycline; D004318:Doxycycline