The tetracycline derivative minocycline differentially affects cytokine production by monocytes and T lymphocytes.
Minocycline is a tetracycline derivative that has beneficial effects in noninfectious forms of arthritis and dermatitis. To investigate whether this effect may be attributed to interference with cytokine production, we studied the effect of minocycline on cytokine production by T cells and monocytes. Minocycline exerted an inhibitory effect on tumor necrosis factor alpha (TNF-alpha) and gamma interferon production by stimulated T cells, whereas the production of interleukin 6 (IL-6) remained unaffected. The effect of minocycline on TNF-alpha mRNA synthesis by T cells was shown to be stimulus specific. T cells stimulated by a Ca2+-independent mode exhibited a decrease in TNF-alpha mRNA in the presence of minocycline, whereas the TNF-alpha mRNA level remained unaffected by minocycline when cells were stimulated in a Ca2+-dependent manner. In contrast to the effect on T cells, addition of minocycline to lipopolysaccharide-stimulated monocytes led to a dose-dependent increase in TNF-alpha and IL-6 production which was paralleled by an enhancement of TNF-alpha mRNA synthesis. These results indicate that minocycline exerts differential effects on the regulation of cytokine production by T cells and monocytes that are partly reflected at the mRNA level. Given the pleiotropic effects of minocycline, it is suggested that the immunostimulatory effect on monocytes might counteract its beneficial properties in the treatment of several forms of chronic inflammation.
Kloppenburg
M
M
Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Brinkman
B M
BM
de Rooij-Dijk
H H
HH
Miltenburg
A M
AM
Daha
M R
MR
Breedveld
F C
FC
Dijkmans
B A
BA
Verweij
C
C
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008911:Minocycline; D013755:Tetradecanoylphorbol Acetate