Intra-articular corticoid injection induces circulating glucocorticoid bioactivity and systemic immune activation in juvenile idiopathic arthritis

Abstract

Objective: To study the systemic effects of intra-articular (IA) glucocorticoid (GC) injections in juvenile idiopathic arthritis (JIA).

Methods: The study group comprised 21 JIA patients being treated with IA methylprednisolone [MP (n = 15) or MP plus triamcinolone hexacetonide (THA) (n = 6)] prescribed on clinical indications. The systemic effect of MP was assessed by measuring circulating glucocorticoid bioactivity (GBA) with a recombinant cell transactivation assay 7 and 24 h after the IA injections, and after 2 months. The systemic immunological responses were studied with a novel assay for testing patient serum-induced changes in the secretion of interferon (IFN)-γ and interleukin (IL)-5 from target cells.

Results: Administration of IA GC induced serum GBA (p = 0.001) and suppressed circulating cortisol levels (p = 0.002) 7 h after the injection. Serum withdrawn 24 h after the IA injection induced less IL-5 secretion from mitogen-activated target cells when compared with pre-treatment sera (p = 0.036). This decrease in target cell T helper (Th)2 response (IL-5) was MP dose related (r = −0.550, p = 0.018). High IL-5 secretion from target cells prior to the IA injections was associated with good clinical outcome at 2 months, seen as a low number of active (p = 0.044) and restricted joints (p = 0.049).

Conclusion: IA GC injections have systemic effects that are reflected in the serum as an immediate elevation of GBA, a decrease of endogenous cortisol as well as a suppressive effect of patient serum on target cell IL-5 secretion. These systemic effects may play a role in the attenuation of disease activity.

Acknowledgements

This study was carried out with the financial support of the Finnish Cultural Foundation, the Finnish Paediatric Research Foundation, the Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital Research Foundation, and the Orion Research Foundation. We thank Sari Honkanen, Minna Kuurne-Koivisto, and Anne Ramstadt for their help in collecting the patient data.