The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and protein secretion in human endothelial cells.
Interactions between interleukin 8 (IL-8) and endothelial cells play an important role in the emigration of mononuclear cells from the blood into areas of inflammation. We examined the ability of specific second-line antirheumatic drugs to regulate (IL-8) gene expression and protein secretion in interleukin 1 (IL-1) stimulated human umbilical vein endothelial cells and peripheral blood mononuclear cells. The drugs sodium aurothiomalate, D-penicillamine and sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein secretion from endothelial cells. A bimodal effect was observed: at low concentrations IL-8 was suppressed, whereas higher concentrations resulted in an increased IL-8 production. In endothelial cells, treatment with hydrocortisone led to a linear suppression of IL-8 production in concentrations ranging from 0.5 micrograms/ml up to 500 micrograms/ml. Sulphapyridine, auranofin, hydroxychloroquine and methotrexate, had no effect on IL-8 secretion in endothelial cells. By contrast, 5-aminosalicylic acid induced a threefold increase in the IL-8 release. In peripheral blood mononuclear cells it was only possible to suppress the IL-8 production by hydrocortisone treatment. These results indicate that suppression of IL-8 production in endothelial cells could be an important factor in the mode of action for a number of second-line antirheumatic drugs.
Deleuran
B
B
Department of Dermatology, Marselisborg Hospital, Aarhus, Denmark.
Kristensen
M
M
Paludan
K
K
Zachariae
C
C
Larsen
C G
CG
Zachariae
E
E
Thestrup-Pedersen
K
K
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D010396:Penicillamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012460:Sulfasalazine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D006052:Gold Sodium Thiomalate; D012460:Sulfasalazine; D010396:Penicillamine; D006854:Hydrocortisone