caa a22 4500 469116021 CHVBK 20180323133125.0 cr unu---uuuuu 170328e19921201xx s 000 0 eng 10.1007/BF02755882 doi (NATIONALLICENCE)springer-10.1007/BF02755882 The effect of slow acting antirheumatic drugs on the production of cytokines by human monocytes [Elektronische Daten] [V. Danis, D. Rathjen, P. Brooks] The mode of action of slow acting antirheumatic drugs (SAARDs) is poorly understood. Interleukin (IL)-1α, IL-1β, IL-6 and tumour necrosis factor (TNF)α are pleiotropic cytokines produced predominantly by macrophages which have been implicated in the pathogenesis of rheumatoid arthritis. We have investigated the potential of the following drugs to modulate the production of those cytokines by purified human monocytes stimulated by either lipopolysaccharide (LPS) or cytokines in vitro: gold sodium thiomalate (GST), auranofin, hydroxychloroquine (HCQ),d-penicillamine (d-Pen), sulphasalazine and its metabolites, sulphapyridine and 5-aminosalicylic acid (5-ASA). Auranofin, HCQ and sulphasalazine, at therapeutically relevant concentrations, inhibited the production of all four cytokines in vitro. There were some differential effects suggesting that HCQ was less effective at inhibiting cell-associated IL-1 production compared with IL-1 release, and the reverse seemed to be the case for sulphasalazine which did not inhibit IL-1 secretion as effectively as cell-associated IL-1 production. Sulphasalazine was also less effective at inhibiting IL-6 production compared with the other three cytokines. GST had only a minor inhibitory effect (on IL-1β release) andd-Pen, sulphapyridine and 5-ASA did not inhibit cytokine production. Finally, low concentrations of gold compounds (GST and auranofin) stimulated IL-1 and IL-6 production directly and potentiated IL-1, IL-6 and TNFα production induced by LPS. These results suggest that some SAARDs may inhibit cytokine production as part of their antirheumatic effect and that the enhancement of cytokine production by low doses of gold may potentially exacerbate rheumatoid disease at the early stages of chrysotherapy. Kluwer Acedemic Publishers, 1992 interleukin-1 nationallicence tumour necrosis factor-α nationallicence interleukin-6 nationallicence SAARDs nationallicence monocytes nationallicence Danis V. Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia aut Rathjen D. Peptide Technology Ltd, Dee Why, Australia aut Brooks P. St Vincents Hospital, Sydney, Australia aut InflammoPharmacology Birkhäuser-Verlag 1/4(1992-12-01), 315-327 0925-4692 1:4<315 1992 1 10787 https://doi.org/10.1007/BF02755882 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02755882 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Danis V. Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia aut NATIONALLICENCE 700 1- Rathjen D. Peptide Technology Ltd, Dee Why, Australia aut NATIONALLICENCE 700 1- Brooks P. St Vincents Hospital, Sydney, Australia aut NATIONALLICENCE 773 0- InflammoPharmacology Birkhäuser-Verlag 1/4(1992-12-01), 315-327 0925-4692 1:4<315 1992 1 10787 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer