Extended reports
The immune suppressive effect of dexamethasone in rheumatoid
arthritis is accompanied by upregulation of interleukin 10 and by
differential changes in interferon 
and interleukin 4 production
Department of
Rheumatology and Clinical Immunology, University Medical Centre
Utrecht, the Netherlands
Correspondence to: Dr C M Verhoef, Department of Rheumatology and Clinical Immunology (F02.127), University Medical Centre, Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Accepted for publication 8 October 1998
OBJECTIVES
The
influence of dexamethasone on interleukin 10 (IL10) production and the
type 1 (T1)/type 2 (T2) T cell balance found in rheumatoid arthritis
(RA) was studied.
METHODSPeripheral
blood mononuclear cells (PB MNC) were isolated from 14 RA patients both
before and 7 and 42 days after high dose dexamethasone pulse therapy.
The ex vivo production of IL10, interferon 
(IFN) (T1 cell), and
IL4 (T2 cell) by PB MNCs was assessed, along with parameters of disease
activity (erythrocyte sedimentation rate, C reactive protein, Visual
Analogue Scale, Thompson joint score). In addition, the in vitro effect
of dexamethasone (0.02, 0.2, and 2 µM) on PB MNC IL10, IFN, and
IL4 production was studied.
RESULTSDexamethasone
pulse therapy resulted in a rapid and sustained decrease in RA disease
activity. IL10 production increased after dexamethasone treatment and
this was sustained for at least six weeks. A transient strong decrease
in IFN was seen shortly after corticosteroid treatment, while IL4
only decreased slightly. This led to an increased IL-4/IFN ratio. In
vitro, IL10 production was not detectable, IFN and IL4 decreased,
but the effect was more pronounced for IFN than for IL4, which again
resulted in an increased IL4/IFN ratio.
CONCLUSIONDexamethasone
therapy in RA patients leads to a rapid, clinically beneficial effect.
The upregulation of IL10 production may be involved in the prolonged
clinical benefit. The strong immunosuppressive effect is most evident
in the decrease in IFN, and is therefore accompanied by a relative
shift towards T2 cell activity. In vitro evaluation showed that this
shift in T cell balance was a direct effect of dexamethasone and thus
independent of the hypothalamic-pituitary-adrenal axis.
;
interleukin 4;
interleukin 10
© 1999 by Annals of the Rheumatic Diseases
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