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

Objectives-A generalised transient improvement may follow intra-articular a dministration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid r eleased from the joint, mediated through processes such as altered leucocyt e trafficking or suppressed release of pro-inflammatory cytokines. Patients , who had received intraarticular injections of glucocorticoids were theref ore studied for evidence of these two systemic effects. Methods-Patients with rheumatoid arthritis were studied. Peripheral blood l eucocyte counts, tumour necrosis factor a (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolo ne concentration were measured for 96 hours after intraarticular injection of methylprednisolone acetate. Results-Measurable concentrations of methylprednisolone were present in blo od for up to 96 hours after injection. Significant suppression of the hypot halamic-pituitary-adrenal axis persisted throughout this time. Altered mono cyte and lymphocyte trafficking, as evidenced by peripheral blood monocytop enia and lymphopenia, was apparent by four hours after injection and resolv ed in concordance with the elimination of methylprednisolone. Granulocytosi s was observed at 24 and 48 hours. Release of TNF alpha by endotoxin stimul ated peripheral blood monocytes was suppressed at four hours and thereafter . Suppression was maximal at eight hours and was largely reversed by the gl ucocorticoid antagonist, mifepristone. Conclusions-After intra-articular injection of methylprednisolone, blood co ncentrations of glucocorticoid are sufficient to suppress monocyte TNF alph a release for at least four days and to transiently alter leucocyte traffic king. These effects help to explain the transient systemic response to intr a-articular glucocorticoids. Suppression of TNF alpha is principally a dire ct glucocorticoid effect, rather than a consequence of other methylpredniso lone induced changes to blood composition.