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


METHODS
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.


METHODS
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).


METHODS
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)-alpha, interleukin (IL)-1beta 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.


CONCLUSIONS
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-1beta, IL-6 and TNF-alpha 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.
MacRae
V E
VE
Department of Child Health, Royal Hospital for Sick Children, Glasgow, UK.
Wong
S C
SC
Smith
W
W
Gracie
A
A
McInnes
I
I
Galea
P
P
Gardner-Medwin
J
J
Farquharson
C
C
Ahmed
S F
SF
D000293:Adolescent; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001171:Arthritis, Juvenile / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001798:Blood Proteins / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D019902:Chondrocytes / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D006130:Growth Disorders / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008682:Metatarsal Bones / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009924:Organ Culture Techniques; D013582:Synovial Fluid / Q000276:immunology* / Q000378:metabolism
D057134:Antibodies, Neutralizing; D001798:Blood Proteins; D016207:Cytokines; D007334:Insulin-Like Growth Factor I