SFEBES2007 Poster Presentations Growth and development (10 abstracts)
1Bone and Endocrine Reaearch Group, Royal Hospital for Sick Children Yorkhill, Glasgow, United Kingdom; 2Bone Biology Group, Roslin Institute, Roslin, United Kingdom; 3Centre for Rheumatic Diseases, University of Glasgow, Glasgow, United Kingdom; 4Department of Child Health, Royal Hospital for Sick Children Yorkhill, Glasgow, United Kingdom.
Background: Inflammatory cytokines in children with juvenile idiopathic arthritis (JIA) may modulate growth through systemic and local mechanisms.
Aims: To study the relationship between inflammatory cytokines in serum /synovial fluid (SF) with growth and to assess the effects of serum/SF on the fetal rat metatarsal model.
Subjects & Methods: 17 children with JIA (F,10): 8 oligoarticular, 2 extended oligoarticular, 6 polyarticular and 1 systemic JIA were recruited at therapeutic arthrocentesis. Samples from 7 of the children (7 serum, 4 SF) were exposed to fetal rat metatarsals over 9 days.
Results: Median age was 6.5 years (2.9, 14.9), median adjusted height (AHt) SDS −0.3 (−2.2, 1.6). Serum ALS SDS (median −1.3, range −2.7, −0.6) was disproportionately lower compared with IGF1 SDS (median −0.2, range −0.5, 0.5) and IGFBP3 SDS (median −0.5, range −1.6, −0.1). Log serum IL5 (95% CI −3.25, −0.81) and log serum IL15 (95% CI −9.58, −4.10) were independent factors associated with AHt SDS. No single one inflammatory cytokine show an association with IGF1, IGFBP1,2,3 and ALS. All 7 serum samples significantly reduced metatarsal growth. Only 2 SF samples (1 systemic, 1 oligoarticular) reduced metatarsal growth. No improvement in bone growth was observed when metatarsals exposed to SF from the child with systemic JIA were exposed to neutralising antibodies to TNFα, IL-1β and IL-6 either individually or in combination.
Conclusion: Growth retardation in JIA is associated with raised levels of serum IL5 and IL15. Low ALS with relatively low IGFBP3 but normal IGF1 suggests a combined state of relative GH and IGF1 resistance systemically. Both serum and SF samples can impair metatarsal growth suggesting a local growth plate effect but this is not reversed with treatment with neutralising antibodies to TNFα, IL-1β and Il-6. Inflammatory cytokines in JIA can therefore affect growth either systemically or at the growth plate.