Abstract
RP 54745 is an amino-dithiole-one compound found to be active at micromolar concentration on the metabolism of stimulated macrophages, for example, the hexose monophosphate pathway (HMP) and the exocytosis of lysosomal enzymes. LPS-induced interleukin-1 (IL-1) production by murine peritoneal macrophages was also diminished by this compoundin vitro as well asin vivo. This effect was confirmed at the mRNA level; at the concentration of 3×10−6 M, the IL-1α and β mRNA signals were inhibited, whereas the TNFα mRNA signal was only slightly lessened. These observations were confirmedin vivo, with a dose of RP 54745 of 25 mg kg−1. These results led us to consider that RP 54745 might influence certain cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
C. A. Dinarello,Biology of Interleukin I. FASEB J.2, 108–115 (1988).
J. Schnyder and M. Baggiolini,Role of phagocytosis in the activation of macrophages. J. Exp. Med.148, 1449–1457 (1978).
P. S. Ringrose, M. A. Parr and M. McLaren,Effects of antiinflammatory and other compounds on the release of lysosomal enzymes from macrophages. Biochem. Pharmacol.24, 607–614 (1975).
I. Gery, R. K. Gershon and B. H. Waksman,Potentiation of the T-lymphocyte response to mitogens. I. The responding cells. J. Exp. Med.136, 128–142 (1972).
P. Chomczynski and N. Sacchi,Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem.162, 156 (1987).
E. Hétier, J. Ayala, P. Denèfle, A. Bousseau, P. Rouget, M. Mallat and A. Prochiantz,Brain macrophages synthesize II 1 and II 1 mRNAs in vitro. J. Neurosci. Res.21, 391–396 (1988).
M. Ziff,Rheumatoid Arthitis—Its Present and Future. J. Rheumatol.17, 127–133 (1990).
G. Firestein and N. Zvaifler,How important are T cells in chronic rheumatoid synovitis? Arth. Rheum.33, 768–773 (1990).
M. Feldmann et al..Cytokines assays: Role in evaluation of the pathogenesis of autoimmunity Immunol. Rev.119, 105–123 (1991).
W. P. Arend and J. M. Dayer,Cytokines and cytokines inhibitors of antagonists in rheumatoid arthritis. Arth. Rheum.33, 305–315 (1990).
D. M. Chang, P. Baptiste, and P. Schur,The effect of antirheumatic drugs on Il-1 activity and Il-1 production by human monocytes. J. Rheumatol.17, 1148–1157 (1990).
S. H. Zuckerman, G. Evans and L. Butler,Endotoxin tolerance: Independent regulation of IL-1 and TNF Expression. Infect. Immun.59, 2774–2780 (1991).
I. Grey, P. Davies, J. Derr, N. Krett and J. A. Barranger,Relationship between production and release of II 1 by murine macrophages. I. Effect of various agents. Cell. Immunol.64, 293–303 (1981).
S. Narumi and T. A. Hamilton,Dexamethasone selectively regulates LPS-inducible gene expression in murine peritoneal macrophages. Immunopharmacology19, 93–101 (1990).
S. H. Zuckerman, G. Evans and L. Guthrie,Transcriptional and post-transcriptional mechanisms involved in the differential expression of LPS-induced IL-1 and TNF mRNA. Immunology73, 460–465 (1991).
O. Otterness, M. Bliven, J. Downs and D. Hanson,Effects of CP-66248 on Il-1 synthesis by murine peritoneal macrophages. Arth. Rheum.31 (Suppl.), 90 (1988).
J. Lee, D. Griswold, B. Votta and N. Hanna,Inhibition of monocyte Il-1 production by the anti-inflammatory compound, SK&F 86002. Int. J. Immunopharmacol.10, 835–843 (1988).
J. Schnyder, P. Bollinger and T. Payne,Inhibition of Il-1 release by IX 207-887. Agents and Actions30, 350–362 (1990).
M. Tanaka et al.,3-(5 Alkyl-4-hydroxyl-3-methoxy-1-naphtalenyl)-2-methyl-2-propenoic acids as orally active inhibitors of IL-1 generation J. Med. Chem.34, 2647–2649 (1991).
R. Rist and R. Naftalin,Dexamethasone inhibits the hexose monophosphate shunt in activated rat peritoneal macrophages by reducing hexokinase-dependent sugar uptake. Biochem. J.278, 129–135 (1991).
J. Chayen, L. Bitensky, R. Butcher and B. Cashman,The effect of experimentally induced redox changes on human rheumatoid and non-rheumatoid synovial tissue in vitro. Beitr. Path. Bd.149, 127–144 (1973).
A. Pitsillides, S. Blake, L. Glynn, L. Bitensky and J. Chayen,Amelioration by menadione of the experimentally chronic immune arthritis in the rabbit. Cell Biochem. Funct.8, 221–226 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Folliard, F., Bousseau, A. & Terlain, B. RP 54745, a potential antirheumatic compound. I. Inhibitor of macrophage stimulation and interleukin-1 production. Agents and Actions 36, 119–126 (1992). https://doi.org/10.1007/BF01991239
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01991239