Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors.
Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P < 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.
de Groof
F
F
Department of Pediatrics, Division of Pediatric Intensive Care, Sophia Children's Hospital, Erasmus University Medical Center, 3000 CB Rotterdam, The Netherlands.
Joosten
K F M
KF
Janssen
J A M J L
JA
de Kleijn
E D
ED
Hazelzet
J A
JA
Hop
W C J
WC
Uitterlinden
P
P
van Doorn
J
J
Hokken-Koelega
A C S
AC
D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D010450:Endopeptidases / Q000097:blood; D005260:Female; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008589:Meningococcal Infections / Q000150:complications*; D012772:Shock, Septic / Q000097:blood* / Q000382:microbiology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease