Extended reports
Altered leucocyte trafficking and suppressed tumour necrosis
factor 
release from peripheral blood monocytes after
intra-articular glucocorticoid treatment
a Department of
Pharmacology, University of Western Australia, Nedlands, Western
Australia, b Department of Rheumatology, Sir Charles Gairdner Hospital,
Nedlands, Western Australia, c Department of Clinical Pharmacology and Toxicology, Western
Australian Centre for Pathology and Medical Research, Nedlands, Western
Australia
Correspondence to: Dr D A Joyce, Department of Pharmacology, University of Western Australia, Nedlands, Western Australia, 6907.
Accepted for publication 17 September 1998
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.
METHODSPatients 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 intra-articular injection of
methylprednisolone acetate.
RESULTSMeasurable 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 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.
CONCLUSIONSAfter intra-articular injection of
methylprednisolone, blood concentrations of glucocorticoid are
sufficient to suppress monocyte TNF 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 is principally a direct
glucocorticoid effect, rather than a consequence of other
methylprednisolone induced changes to blood composition.
;
methylprednisolone;
human;
leucocyte trafficking
© 1998 by Annals of the Rheumatic Diseases
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