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

• Published in: Scandinavian journal of rheumatology 2011-10, Vol.40 (5), p.347-353
• Main Authors: Rintamäki, H, Tamm, K, Vaarala, O, Sidoroff, M, Honkanen, V, Raivio, T, Jänne, OA, Kolho, K-L
• Format: Article
• Language: English
• Subjects: Adolescent; Anti-Inflammatory Agents - administration & dosage; Arthritis, Juvenile - drug therapy; Arthritis, Juvenile - immunology; Biological and medical sciences; Child; Diseases of the osteoarticular system; Female; Glucocorticoids - administration & dosage; Glucocorticoids - blood; Humans; Hydrocortisone - blood; Immune System - drug effects; Inflammatory joint diseases; Injections, Intra-Articular; Interferon-gamma - blood; Interferon-gamma - secretion; Interleukin-5 - blood; Interleukin-5 - secretion; Male; Medical sciences; Methylprednisolone - administration & dosage; Methylprednisolone - immunology; Prospective Studies; Th2 Cells - drug effects; Treatment Outcome; Triamcinolone Acetonide - administration & dosage; Triamcinolone Acetonide - analogs & derivatives
• ISSN: 0300-9742; 1502-7732
• DOI: 10.3109/03009742.2011.560893

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 Serum withdrawn 24 h after the IA injection induced less IL-5 secretion from mitogen-activated target cells when compared with pre-treatment sera (p = 0.036).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.