Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis

Macrae, V.E., Wong, S.C. , Smith, W., Gracie, A., McInnes, I., Galea, P., Gardner-Medwin, J., Farquharson, C. and Ahmed, S.F. (2007) Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis. Clinical Endocrinology, 67(3), pp. 442-448. (doi: 10.1111/j.1365-2265.2007.02908.x) (PMID:17555514)

Abstract

Objective: Growth retardation in children with chronic inflammatory disease may be partly due to direct effects of pro-inflammatory cytokines on the growth plate and requires further investigation. Design: This study assessed the cytokine concentrations in serum and synovial fluid (SF) in juvenile idiopathic arthritis (JIA), and determined the effect of the biological fluid on cultured murine metatarsal growth. Patients: Serum and SF were obtained from four children attending for arthrocentesis (child A, systemic; children B, C and D, oligoarticular). In addition, serum samples were obtained from four more children (children E and F, polyarticular; child G, oligoarticular). Measurements: Anthropometry, cytokine levels and longitudinal bone growth were assessed. Results: Cytokines were elevated to a variable extent in the samples. Although all serum samples were associated with reduced metatarsal growth, only SF from child A and child B reduced metatarsal growth. Metatarsals treated with child A's SF showed reduced proliferation, reduced proliferative and mineralizing zone width, and increased hypertrophic zone width. Tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 concentrations were elevated in child A's SF. However, SF exposure with neutralizing antibodies to these cytokines or IGF-1 did not improve metatarsal growth. Conclusion: SF and serum JIA samples can impair bone growth at the growth plate. In synovial fluid, the effect is variable but resistant to treatment with IL-1β, IL-6 and TNF-α specific antibodies and IGF-1, suggesting that other factors in this biological fluid may also have an effect on longitudinal growth through IGF-1-independent mechanisms.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Wong, Dr Jarod and Gardner-Medwin, Dr Janet and Ahmed, Professor Syed Faisal
• Authors: Macrae, V.E., Wong, S.C., Smith, W., Gracie, A., McInnes, I., Galea, P., Gardner-Medwin, J., Farquharson, C., and Ahmed, S.F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
• Journal Name: Clinical Endocrinology
• Journal Abbr.: Clin Endocrinol
• Publisher: Blackwell Publishing Ltd
• ISSN: 0300-0664
• ISSN (Online): 1365-2265
• Published Online: 19 May 2007
• Published Online: 19 May 2007