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Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release from peripheral blood monocytes
1Department of Pharmacology, University of Western Australia, Nedlands, Western Australia.
Objectives:
A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects.
Methods:
Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intra-articular 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 trafficking, 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 alpha 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 sufficient to suppress monocyte TNF alpha release for at least four days and to transiently alter leucocyte trafficking. These effects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF alpha is principally a direct glucocorticoid effect, rather than a consequence of other methylprednisolone induced changes to blood composition.