Affiliation:
1. Department of Rheumatology, University Hospital, Leiden, The Netherlands.
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference51 articles.
1. Differential induction of interleukin-6 production in monocytes, endothelial cells and smooth muscle cells;Aarden L. A.;Eur. Cytokine Network,1991
2. Avidity of the tetracyclines for the cations of metals;Albert A.;Nature (London),1956
3. Antibiotics and suppression of Iymphocyte function in vitro;Banck G.;Antimicrob. Agents Chemother.,1979
4. Tetracyclines modulate cytosolic Ca2~ responses in the osteoclast associated with ``Ca2~ receptor'' activation. Biosci;Bax C. M. R.;Rep.,1993
5. Lipopolysaccharide-induced cytokine production in human monocytes: role of tyrosine phosphorylation in transmembrane signal transduction;Beaty C. D.;Eur. J. Immunol.,1994
Cited by
97 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献