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. 1990 Mar;79(3):335–340. doi: 10.1111/j.1365-2249.1990.tb08092.x

The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleukin-1 production by blood monocytes in vitro: variation in healthy subjects and patients with arthritis.

V A Danis 1, A J Kulesz 1, D S Nelson 1, P M Brooks 1
PMCID: PMC1534945  PMID: 2107989

Abstract

The anti-rheumatic gold compounds gold sodium thiomalate (GST) and auranofin (AF) have variable and often unpredictable effects in patients treated for arthritis. As inhibition of interleukin-1 (IL-1) production may be an important effect of these drugs, we investigated their effect on IL-1 production by lipopolysaccharide (LPS) stimulated monocytes in a serum-free, non-adherent culture system. A bi-modal effect was observed: low concentrations (GST 10-250 ng/ml and AF 1-100 ng/ml) potentiated IL-1 production, and higher concentrations (GST 200-1000 ng/ml and AF10-500 ng/ml) inhibited it. This bi-modal effect was observed for both secreted and cell-associated IL-1 activity with the exception that GST failed to inhibit cell-associated IL-1 generation. The potentiating effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory effect of GST was dependent on its presence after LPS stimulation while that of AF was evident even if cells were pretreated with AF and washed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in the effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold that potentiated and inhibited IL-1 production, and there was relative insensitivity to the inhibitory effects of gold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effects might predict clinical response to gold.

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Selected References

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  1. Barrett M. L., Lewis G. P. Unique properties of auranofin as a potential anti-rheumatic drug. Agents Actions. 1986 Oct;19(1-2):109–115. doi: 10.1007/BF01977265. [DOI] [PubMed] [Google Scholar]
  2. Champion G. D., Cairns D. R., Bieri D., Adena M. A., Browne C. D., Cohen M. L., Day R. O., Edmonds J. P., Graham G. G., de Jager J. Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis. J Rheumatol. 1988 Jan;15(1):28–34. [PubMed] [Google Scholar]
  3. Conlon P. J., Grabstein K. H., Alpert A., Prickett K. S., Hopp T. P., Gillis S. Localization of human mononuclear cell interleukin 1. J Immunol. 1987 Jul 1;139(1):98–102. [PubMed] [Google Scholar]
  4. Dahl S. L., Coleman M. L., Williams H. J., Altz-Smith M., Kay D. R., Paulus H. E., Weinstein A., Kaplan S. Lack of correlation between blood gold concentrations and clinical response in patients with definite or classic rheumatoid arthritis receiving auranofin or gold sodium thiomalate. Arthritis Rheum. 1985 Nov;28(11):1211–1218. doi: 10.1002/art.1780281104. [DOI] [PubMed] [Google Scholar]
  5. Danis V. A., Kulesz A., Nelson D. S., Brooks P. M. Bimodal effect of gold on IL-1 production by blood monocytes. J Rheumatol. 1989 Aug;16(8):1160–1161. [PubMed] [Google Scholar]
  6. Danis V. A., March L. M., Nelson D. S., Brooks P. M. Interleukin-1 secretion by peripheral blood monocytes and synovial macrophages from patients with rheumatoid arthritis. J Rheumatol. 1987 Feb;14(1):33–39. [PubMed] [Google Scholar]
  7. Davies P., Bonney R. J., Humes J. L., Kuehl F. A., Jr The effect of anti-rheumatic agents on macrophage function. Int J Immunopharmacol. 1982;4(2):111–118. doi: 10.1016/0192-0561(82)90058-3. [DOI] [PubMed] [Google Scholar]
  8. Drakes M. L., Harth M., Galsworthy S. B., McCain G. A. Effects of gold on the production of and response to human interleukin-1. J Rheumatol. 1987 Dec;14(6):1123–1127. [PubMed] [Google Scholar]
  9. Eastgate J. A., Symons J. A., Wood N. C., Grinlinton F. M., di Giovine F. S., Duff G. W. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet. 1988 Sep 24;2(8613):706–709. doi: 10.1016/s0140-6736(88)90185-7. [DOI] [PubMed] [Google Scholar]
  10. Endres S., Ghorbani R., Lonnemann G., van der Meer J. W., Dinarello C. A. Measurement of immunoreactive interleukin-1 beta from human mononuclear cells: optimization of recovery, intrasubject consistency, and comparison with interleukin-1 alpha and tumor necrosis factor. Clin Immunol Immunopathol. 1988 Dec;49(3):424–438. doi: 10.1016/0090-1229(88)90130-4. [DOI] [PubMed] [Google Scholar]
  11. Henderson B., Pettipher E. R., Higgs G. A. Mediators of rheumatoid arthritis. Br Med Bull. 1987 Apr;43(2):415–428. doi: 10.1093/oxfordjournals.bmb.a072191. [DOI] [PubMed] [Google Scholar]
  12. Hopkins S. J., Humphreys M., Jayson M. I. Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1. Clin Exp Immunol. 1988 Jun;72(3):422–427. [PMC free article] [PubMed] [Google Scholar]
  13. Kean W. F., Forestier F., Kassam Y., Buchanan W. W., Rooney P. J. The history of gold therapy in rheumatoid disease. Semin Arthritis Rheum. 1985 Feb;14(3):180–186. doi: 10.1016/0049-0172(85)90037-x. [DOI] [PubMed] [Google Scholar]
  14. Kern J. A., Lamb R. J., Reed J. C., Daniele R. P., Nowell P. C. Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. J Clin Invest. 1988 Jan;81(1):237–244. doi: 10.1172/JCI113301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knudsen P. J., Dinarello C. A., Strom T. B. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cells. J Immunol. 1987 Dec 15;139(12):4129–4134. [PubMed] [Google Scholar]
  16. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  17. Matsubara T., Saegusa Y., Hirohata K. Low-dose gold compounds inhibit fibroblast proliferation and do not affect interleukin-1 secretion by macrophages. Arthritis Rheum. 1988 Oct;31(10):1272–1280. doi: 10.1002/art.1780311009. [DOI] [PubMed] [Google Scholar]
  18. Maury C. P., Andersson L. C., Teppo A. M., Partanen S., Juvonen E. Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin 1 beta concentrations in anaemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro. Ann Rheum Dis. 1988 Dec;47(12):972–978. doi: 10.1136/ard.47.12.972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mosley B., Dower S. K., Gillis S., Cosman D. Determination of the minimum polypeptide lengths of the functionally active sites of human interleukins 1 alpha and 1 beta. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4572–4576. doi: 10.1073/pnas.84.13.4572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mølvig J., Baek L., Christensen P., Manogue K. R., Vlassara H., Platz P., Nielsen L. S., Svejgaard A., Nerup J. Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. Scand J Immunol. 1988 Jun;27(6):705–716. doi: 10.1111/j.1365-3083.1988.tb02404.x. [DOI] [PubMed] [Google Scholar]
  21. Remvig L., Enk C., Bligaard N. Effect of auranofin and sodium aurothiomalate on interleukin-1 production from human monocytes in vitro. Scand J Rheumatol. 1988;17(4):255–262. doi: 10.3109/03009748809098794. [DOI] [PubMed] [Google Scholar]
  22. Schmidt J. A., Abdulla E. Down-regulation of IL-1 beta biosynthesis by inducers of the heat-shock response. J Immunol. 1988 Sep 15;141(6):2027–2034. [PubMed] [Google Scholar]
  23. Singer I. I., Scott S., Hall G. L., Limjuco G., Chin J., Schmidt J. A. Interleukin 1 beta is localized in the cytoplasmic ground substance but is largely absent from the Golgi apparatus and plasma membranes of stimulated human monocytes. J Exp Med. 1988 Feb 1;167(2):389–407. doi: 10.1084/jem.167.2.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zurovsky Y., Laburn H. P., Mitchell D., Ruck A. Sodium aurothiomalate does not block interleukin 1 production in rabbits. Ann Rheum Dis. 1988 Jun;47(6):506–508. doi: 10.1136/ard.47.6.506. [DOI] [PMC free article] [PubMed] [Google Scholar]

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