INSULIN-LIKE GROWTH-FACTORS (IGFS) AND IGF-BINDING PROTEINS IN HUMAN SKIN INTERSTITIAL FLUID

Despite extensive investigation of the insulin-like growth factor (IGF )/IGF-binding protein (IGFBP) system in the circulation and body fluid s, there is no information on this in interstitial fluid. We have comp ared the IGF/IGFBP system in the circulation with that in fluid obtain ed from blisters artificially raised by negative pressure in 10 health y volunteers. IGFBP-1, -2, -3, and -4 were all found in blister fluid; but in concentrations much lower than those in matched serum. The IGF -I, IGF-II, and IGFBP-3 levels measured by RIA were 18%, 14%, and 16% of those in serum, respectively. Fast protein liquid chromatography sh owed that both IGF-I and IGFBP-3 in 150- and 50-kilodalton complexes w ere approximately 13% and 37%, respectively, of the corresponding peak s found in matched serum. Compared to that in serum, the IGFBP-3 in th e blister fluid was predominantly in a modified as-kilodalton form, an d there was increased activity of an IGFBP-3 protease; Therefore, alth ough IGF concentrations are much lower in interstitial fluid than in t he circulation, a greater proportion of this IGF is in forms more read ily available for interaction with tissue receptors. The blister fluid appears to represent physiological interstitial fluid and may provide a model for studying the physiology and pathophysiology of growth fac tors in the interstitial environment.