Increased levels of IGF-1 and beta2-microglobulin in epithelial lining fluid of preterm newborns developing chronic lung disease. effects of rhG-CSF.
Insulin-like growth factor-1 (IGF-1) is involved in regulating the Th-1/Th-2 balance, favoring the development of the Th-2 compartment which enhances fibrosis, one of the main characteristics of Chronic Lung Disease (CLD) in premature newborns. Limited data is available concerning a possible association between early epithelial lining fluid (ELF) concentrations of IGF-1 (total and free forms), IGF-binding protein-3 (IGFBP-3), beta2-microglobulin and subsequent development of CLD in preterm neonates. If neutropenic, preterm neonates are frequently treated with recombinant human granulocyte colony stimulating factor (rhG-CSF). The objective of the study was to correlate ELF concentrations of IGF-1 and beta2 microglobulin during the first week of life both in non-neutropenic and in rhGCSF-treated neutropenic preterm neonates, with subsequent development in CLD. Thirty preterm neonates with Respiratory Distress Syndrome (6 with neutropenia) were studied. Eleven out of 24 non-neutropenic preterm infants (46%) and all of the six neutropenic subjects (100%) developed CLD. With the exception of first day values, there was a clear similarity in the behaviors of assayed molecules between non-neutropenic and neutropenic patients developing CLD. Non-neutropenic patients without CLD showed significantly lower values of free IGF-1 and beta2M both on days 1 and 3. Total IGF-I and cell counts were different only on the 3rd day.


CONCLUSIONS
1) the mechanisms leading to CLD might be mediated by high levels of IGF-family molecules soon after birth 2) beta2M could be a marker of increased bronchoalveolar lavage fluid cellularity with potential inflammatory properties 3) G-CSF treatment induces an increased synthesis of IGF-1 molecules by cells recruited in the lung, with possible enhancement of the fibrogenic mechanisms.
Capoluongo
E
E
Biochemistry and Clinical-Biochemistry Institute, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy. ecapoluongo@rm.unicatt.it
Vento
G
G
Ameglio
F
F
Lulli
P
P
Matassa
P G
PG
Carrozza
C
C
Santini
S A
SA
Antenucci
M
M
Castagnola
M
M
Giardina
B
B
Romagnoli
C
C
Zuppi
C
C
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002690:Chlamydia Infections / Q000188:drug therapy / Q000382:microbiology; D002908:Chronic Disease; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D009503:Neutropenia / Q000188:drug therapy / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D011994:Recombinant Proteins; D016869:Ureaplasma Infections / Q000188:drug therapy / Q000382:microbiology; D016990:Ureaplasma urealyticum; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D016179:Granulocyte Colony-Stimulating Factor; D007334:Insulin-Like Growth Factor I