Altered leucocyte trafficking and suppressed tumour necrosis factor alpha  release from peripheral blood monocytes after intra-articular glucocorticoid treatment

Abstract

Objectives-A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory eVect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte traYcking or suppressed release of pro-inflammatory cytokines. Patients, who had received intraarticular injections of glucocorticoids were therefore studied for evidence of these two systemic eVects. Methods-Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor (TNF ) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intraarticular injection of methylprednisolone acetate. Results-Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte traYcking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone. Conclusions-After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are suYcient to suppress monocyte TNF release for at least four days and to transiently alter leucocyte traYcking. These eVects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF is principally a direct glucocorticoid eVect, rather than a consequence of other methylprednisolone induced changes to blood composition.

Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice

“…Glucocorticoids (e.g. corticosterone) modulate antigen presentation, cytokine production, T-cell expansion, and natural killer cell activity (Belsito et al, 1982;Snyder and Unanue, 1982;Chrousos and Gold, 1992;Bonneau et al, 1997;Maes et al, 1998;Steer et al, 1998;Wiegers and Reul, 1998). Thus, stress causes various disorders in relation to bio-regulatory, autonomic nervous, endocrine and immune system.…”

Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammatory conditions

“…The function of these cells in RA is controversial: several studies have found no alteration in neutrophil function, and others have pointed out different abnormalities in migratory activity, phagocytosis, or oxidative burst [18 -24]. Determining the influence of different therapies on phagocyte function has been the objective of several studies in patients with RA [21,22,[25][26][27][28][29], although the impact of the disease itself on phagocyte function has rarely been addressed [20,30].…”

Targets of glucocorticoid action on TNF-α release by macrophages

“…The effects on monocyte/macrophages (Mf) include altered trafficking [2,3], monokine release [2 -4], surface Inflamm. res.…”

“…50 (2001) 337 -340 1023-3830/01/070337-04 $ 1.50+0.20/0 receptors expression and shedding [5] and lipid mediator release [6]. Mf-derived TNF-a is particularly important in the pathogenesis of many inflammatory diseases [7] and is subject to regulation by glucocorticoids in-vivo [2,3].…”