Impaired Glucocorticoid Induction of Mononuclear Leukocyte Lipocortin‐1 in Rheumatoid Arthritis

Abstract

Objective. To investigate leukocyte lipocortin-1 production in rheumatoid arthritis (RA).Methods. Eight control and 8 RA subjects received 100 mg hydrocortisone intravenously. Leukocyte lipocortin-1 was measured by enzyme-linked immunosorbent assay.Results. Hydrocortisone induced significant increases in lipocortin-1 production by control mononuclear cells (MNC) (P = 0.006 versus baseline) but not by RA MNC (P = 0.44 versus baseline). Peak lipocortin-1 levels in control MNC were significantly higher than those in RA MNC (P = 0.014). Conchsion. These results indicate that glucocorticoid-induced MNC lipocortin-1 production is impaired in RA.Glucocorticoid hormones are used widely in the therapy of inflammatory diseases including rheumatoid arthritis (RA). The use of glucocorticoids is associated with not inconsiderable morbidity, but it has continued because of the broad spectrum of antiinflammatory effects these drugs possess. Endogenous

Neuroendocrine-Immune System Interactions and Autoimmunity

“…Cortisol levels decrease significantly with progression of disease, particularly in the context of a disease flare (189). Some RA patients also show evidence of blunted respon siveness (resistance) to corticosteroids (190,191) and have abnormally low levels of corticosteroid re ceptors on peripheral blood mononuclear cells (192). RA patients also have increased beta-adrenergic receptor density and function on their peripheral blood mononuclear cells, suggesting reduced sympathetic nervous system function, which is a major component of the stress response system (193).…”

Annexin I and dexamethasone effects on phospholipase and cyclooxygenase activity in human synoviocytes

“…23 Moreover, altered annexin I biology is seen in subjects with RA, who exhibit reduced numbers of annexin I binding sites on leukocytes compared to controls. 25 Impaired glucocorticoid induction of annexin I production has also been noted in leukocytes of RA patients, 26 and RA patients with high titre antiannexin I antibodies exhibit impaired glucocorticoid responsiveness. 27 Treatment of undifferentiated cells with glucocorticoids increases annexin I transport to the cell surface.…”

Pro- and anti-inflammatory actions in coronary artery disease : with focus on CD56+ T cells and Annexin A1

“…Our findings are in agreement with a study by Solito et al (Solito et al, 2003) demonstrating that 10 -6 M dexamethasone induced an increase in AnxA1 mRNA in a human folliculostellate cell line. Furthermore, earlier in vivo studies have described substantially increased expression of AnxA1 protein in peripheral monocytes or PBMCs in healthy subjects after one single injection of hydrocortisone (Goulding et al, 1990;Morand et al, 1994).…”