Effects of macrolides on antigen presentation and cytokine production by dendritic cells and T lymphocytes.
Macrolides are effective therapeutic agents for chronic respiratory tract diseases, such as chronic sinusitis, sinobronchial syndrome and diffuse panbronchiolitis. Although only limited information is available about their mechanisms, suppression of various inflammatory cytokines (IL-8, etc.) and some transcription factors has been reported to be involved. Non-typeable Haemophilus influenzae (NTHI) is one of the most important pathogens of the respiratory tract. P6 is one of the outer membrane proteins of NTHI and the target antigen of protective antibodies. To analyze the influence of macrolides on human dendritic cells (DCs), we treated DCs with macrolides and used them as antigen-presenting cells (APCs). Clarithromycin, roxithromycin and prednisolone suppressed the in vitro proliferative response of CD4+ T cells to P6 and also the production of cytokines. As a control, we also cultured DCs alone and exposed them to the medicament, while conversely culturing T cells without adding any drugs to the cultures. The results showed similar tendencies for suppression of immune responses. These findings suggest that macrolides suppress the antigen-specific immune responses of DCs in vitro.
Ishida
Yoshiya
Y
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Midorigaoka E2-1-1-1, Asahikawa, Hokkaido, Japan. ishida@asahikawa-med.ac.jp
Abe
Yusuke
Y
Harabuchi
Yasuaki
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D018073:Haemophilus Vaccines / Q000276:immunology*; D006193:Haemophilus influenzae; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis; D018942:Macrolides / Q000494:pharmacology*; D011239:Prednisolone / Q000494:pharmacology; D015575:Roxithromycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D018073:Haemophilus Vaccines; D016209:Interleukin-8; D007378:Interleukins; D018942:Macrolides; C069990:P6 outer membrane protein, Haemophilus; D015575:Roxithromycin; D011239:Prednisolone; D017291:Clarithromycin