Insulin-Like Growth Factor-1 Signaling in Lung Development and Inflammatory Lung Diseases

Table 1

Changes and clinical relevance of serum IGF-1 levels in lung diseases.

	Changes	Clinical relevance	Ref.
BPD	Decreased	Low IGF-1 levels associate with the risk of developing BPD.; A clinical trial (NCT01096784) showed the potential of supplement rhIGF-I/rhIGFBP-3 in reducing the prevalence of BPD in premature infants.	[69, 70]
IPF	Increased	Preclinical studies have shown that inhibition of IGF-1 signaling attenuates experimental pulmonary fibrosis.	[81–92, 146]
ALI/ARDS	Early stage: increased; Late (fibroproliferative) stage: decreased	Low IGF-1 levels associate with the risk of developing ARDS and the mortality of ARDS patients.; Preclinical studies have shown that IGF-1 attenuates experimental lung injury.	[150–154, 168]
Asthma	Increased	Preclinical studies have shown that lung-specific IGF-1R depletion renders mice more asthma-prone, while nonorgan specific IGF-1R protects mice from airway hyperresponsiveness and asthmatic airway inflammation.	[193, 194]
COPD	Decreased in stable stage and decreased more sharply in acute exacerbation	Associated with inflammation, skeletal muscle dysfunction, abnormal metabolism, and weight loss.; Preclinical studies have shown that IGF-1 improves skeletal muscle synthesis and function.	[218–226, 231–245]
Cystic fibrosis	Decreased in stable stage and decreased more sharply in acute exacerbation	Associated with systemic/alveolar inflammation, airway infection, and relative growth hormone insufficiency; associated with growth retardation and metabolic abnormalities.; Prolonged use of IGF-1 has shown efficacy in improving growth and metabolism in a CF child.; A clinical trial of IGF-1 in CF patients was terminated for insufficient enrollment.	[257–268]
Lung cancer	Inconsistent data (increased or decreased)	Serum IGF-1 level is associated with the stage of lung cancer; predictive of resistance to EGFR-TKI therapy.; Clinical trials of IGF-1/IGF-1R mAb/inhibitor have generated results; a few of the results are positive.	[10, 12–16, 269]
ARMS	Insufficient data	IGF-1/IGF-1R-based therapies are to be investigated in clinical trials; presumably drug resistance develops soon with IGF-1R mAb.	[17]

BPD: bronchopulmonary dysplasia. IPF: idiopathic pulmonary fibrosis. ALI/ARDS: acute lung injury/acute respiratory distress syndrome. COPD: chronic obstructive pulmonary disease. EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitor. ARMS: alveolar rhabdomyosarcoma.