IGF-I/IGFBPs system response to endotoxin challenge in sheep

Area of Science:

• Endocrinology
• Metabolic Physiology
• Sepsis Pathophysiology

Background:

• Endotoxin (LPS) from gram-negative bacteria induces sepsis-like endocrine and metabolic effects.
• LPS alters the growth hormone (GH) axis, promoting catabolism, with species-dependent responses.
• Rats show decreased GH, while humans and sheep exhibit increased GH after LPS.

Purpose of the Study:

• To investigate LPS effects on the insulin-like growth factor I (IGF-I)/IGF-binding proteins (IGFBPs) system in rams.
• To analyze the temporal relationship between GH axis changes and hormonal/metabolic parameters (somatostatin, cortisol, insulin, glucose) post-LPS administration.

Main Methods:

• Intravenous administration of a high dose of LPS to intact rams.
• Measurement of plasma total IGF-I, IGFBPs (IGFBP-1, -2, -3, -4) using Western ligand blot.
• Assay of GH, cortisol, insulin, glucose, and somatostatin levels over time.

Main Results:

• LPS induced a delayed decrease in total IGF-I levels (-26.6% at 9h) despite a biphasic, sustained increase in GH secretion.
• An early, transient increase in IGFBP-1 (188.8%) was observed, coinciding with insulin surge; other IGFBPs remained unchanged.
• Marked increases in cortisol and insulin were noted, alongside a sustained rise in somatostatin.

Conclusions:

• Decreased IGF-I and increased IGFBP-1 contrast with elevated GH, indicating endotoxin-induced GH resistance in rams.
• Reduced IGF-I bioavailability may exacerbate the catabolic state observed in sepsis.
• Endotoxin-induced alterations in the IGF-I/IGFBP system likely involve somatostatin, glucocorticoids, and cytokines.