Stimulating effect of growth hormone on cytokine release in children.
OBJECTIVE
The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their relation with IGF-I levels in normal short stature children.


METHODS
23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean+/-s.d. chronological age was 11.95+/-1.85 Years (from 8.80 to 14.89 Years), and mean+/-s.d. bone age was 10.48+/-2.44 Years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex- and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children, and 12 h following the 4th GH subcutaneous injection in the 23 short children only.


RESULTS
No significant differences were found between short children and controls in basal values of serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to 338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; P<0.00001). No significant differences were found between short children and controls in basal concentrations of serum INF-gamma (19+/-4 and 26+/-5 mIU/ml respectively), IL-1alpha (24.950+/-3.613 and 20.896+/-2.778 pg/ml respectively), IL-2 (3.945+/-1.209 and 4.794+/-0.562 pg/ml respectively), IL-12 (1.093+/-0.269 and 1.976+/-0.596 pg/ml respectively), and TNF-alpha (1.794+/-0.559 and 2.188+/-0.346 pg/ml respectively). Likewise, a significant increase was found in serum INF-gamma (before 19+/-4 and after four GH injections 185+/-57 mIU/ml respectively; P<0.008), IL-1beta (24.950+/-3.613 to 43.339+/-5.431 pg/ml respectively; P<0.0001), IL-2 (3.945+/-1.209 to 9.165+/-2.331 pg/ml respectively; P<0.003), IL-12 (1.093+/-0.269 to 3.724+/-0.637 pg/ml respectively; P<0.0007) and TNF-alpha (1.794+/-0.559 to 9.266+/-3.066 pg/ml respectively; P<0.01).


CONCLUSIONS
Cytokine release can be affected by short-term GH administration in normal children indicating a direct influence of GH on the immune system.
Dipartimento di Scienze Pediatriche, Universita degli Studi di Pavia, IRCCS San Matteo, Piazzale le Golgi 2, 27100 Pavia, Italia. m.bozzola@smatteo.pv.it
Mauro
M
Bozzola
Fabrizio
F
De Benedetti
Mara
M
De Amici
Béatrice
B
Jouret
Paola
P
Travaglino
Sara
S
Pagani
Françoise
F
Conte
Maïthé
M
Tauber
D000293:Adolescent; D001827:Body Height; D002648:Child; D016207:Cytokines / Q000097:blood*; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D018664:Interleukin-12; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma