Rheumatology Advance Access published online on January 17, 2006
Rheumatology, doi:10.1093/rheumatology/kei282
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1 Department of Biochemistry, College of Medicine, Catholic University of Korea, Seoul, South Korea
* To whom correspondence should be addressed. Objectives. TNF- Methods. Human peripheral blood mononuclear cells and monocytes/macrophages and monocytic U-937 and THP-1 cells were stimulated with lipopolysaccharide, and TNF- Results. TNF- Conclusions. Our results indicate that chloroquine-mediated inhibition of TNF-
Received August 29, 2005
Accepted November 29, 2005
Original Papers
Chloroquine inhibits production of TNF-
C.-H. Jang 1,
J.-H. Choi 1,
M.-S. Byun 1,
and
D.-M. Jue 1 *
, IL-1
and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes
D.-M. Jue, E-mail: dmjue{at}catholic.ac.kr
Abstract 
, IL-1 and IL-6 are known to have primary roles in the pathogenesis of rheumatoid arthritis and other inflammatory diseases. The anti-rheumatic drug chloroquine has been shown to inhibit TNF-, IL-1 and IL-6 production from mononuclear phagocytes. We examined the underlying mechanisms involved in the chloroquine-induced inhibition of cytokine production., IL-1
and IL-6 production was measured by ELISA. Levels of mRNA were measured by northern blotting and reverse transcription-polymerase chain reaction. Synthesis of 26-kDa TNF- precursor was measured by metabolic labelling and immunoprecipitation analysis. Transcription rate was determined by nuclear run-on assay. release from the cells was inhibited by chloroquine, whereas the steady-state level of TNF- mRNA and synthesis of 26-kDa TNF- precursor were not changed by chloroquine. In contrast, chloroquine-induced inhibition of IL-1 and IL-6 release was accompanied by a decrease in their steady-state mRNA levels. The transcription rates of the IL-1 and IL-6 genes were not changed by chloroquine, whereas the stability of IL-1 and IL-6 mRNA was decreased by chloroquine. Weak-base amines such as methylamine and ammonium chloride had no effect on the production of TNF-, whereas they partially blocked the production of IL-1 and IL-6., IL-1 and IL-6 synthesis occurs through different modes in lipopolysaccharide-stimulated human monocytes/macrophages: it blocks the conversion of cell-associated TNF- precursor to mature soluble protein, whereas it reduces the levels of IL-1 and IL-6 mRNA, at least in part, by decreasing their stability and by a pH-dependent mechanism.
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