Free insulin-like growth factor (IGF)-1 and IGF-binding proteins-2 and -3 in serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients.
BACKGROUND
The insulin-like growth factor-1 (IGF-1) signaling system is regulated by many factors which interact in regulating the bioavailability of IGF-I. In this context, little information is available on free IGF-1, the bioactive form of IGF-1, in amyotrophic lateral sclerosis (ALS).


METHODS
We investigated the endogenous expression of IGF-1, and two related binding proteins (IGF-binding proteins, IGFBP-2 and BP-3) in serum and cerebrospinal fluid (CSF) of 54 sporadic ALS (sALS) patients. Twenty-five healthy individuals and 25 with other neurological diseases (OND) were used as controls. Total and free IGF-1, and IGFBP-3 levels were detected by immunoradiometric assay (IRMA); IGFBP-2 levels were determined by radioimmunoassay (RIA).


RESULTS
Total and free IGF-1, IGFBP-2 and BP-3 serum levels were not significantly different between patients and controls, although in sALS patients free IGF-1 was negatively correlated with ALS-Functional Rating Scale-revised (ALS-FRS-R) score (r = -0.4; P = 0.046) and forced vital capacity (FVC) (r = -0.55; P < 0.04). In CSF, free IGF-1 was significantly increased in sALS patients compared with OND (P < 0.0001).


CONCLUSIONS
Though in the serum we did not find significant differences amongst the three groups, IGF-1 bioavailability, represented by the free IGF-1 levels, correlated with disease severity. In the CSF, the significant increment of the free fraction of IGF-1 suggests an up-regulation of the IGF-1 system in the intrathecal compartment of sALS patients. Since IGF-1 is a trophic factor for different tissues, we speculate that high levels of the free IGF-1 in sALS might reflect a physiological defensive mechanism promoted in response to neural degeneration and/or muscle atrophy.
Department of Neurology and Lab. Neuroscience, 'Dino Ferrari' Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy. massimo.corbo@centrocliniconemo.it
M
M
Corbo
C
C
Lunetta
P
P
Magni
E
E
Dozio
M
M
Ruscica
L
L
Adobbati
V
V
Silani
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D001682:Biological Availability; D005260:Female; D006801:Humans; D015592:Immunoradiometric Assay; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D011863:Radioimmunoassay; D012720:Severity of Illness Index
C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I