Dose-Dependent Impairment of Collagen Deposition by Topical Granulocyte-Macrophage Colony-Stimulating Factor in Human Experimental Wounds

Abstract

ObjectiveThe authors studied the dose-dependent effect of topically administered granulocyte-macrophage colony-stimulating factor (GM-CSF) on the connective tissue response using an experimental repair model in surgical patients. Summary Background DataGM-CSF is primarily indicated in the treatment of immunosuppressed states. The effect of GM-CSF on the tissue repair response in humans is unclear. MethodsExpanded polytetrafluoroethylene tubes were implanted subcutaneously and GM-CSF was applied locally at concentrations of 0.1 g/mL (total dose 0.4 g), 1.0 g/mL (4.0 g), 10 g/mL (40 g), or 75 g/mL (300 g) in one arm and saline alone (control) in the contralateral arm of 56 surgical patients. The content of collagen and total protein in the tubes was quantified as hydroxyproline and proline by high-performance liquid chromatography 10 days after implantation. Cellularity and the number of procollagen I-positive fibroblasts were determined by histology and immunohistochemistry. The direct effects of GM-CSF on collagen production by and proliferation of wound fibroblasts cultured from granulation tissue were also measured.

Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction

“…In an experimental model, inhibition of collagen accumulation, which was induced by osteopontin knock-out, caused excessive infarct expansion during the infarct healing process (18). In human experimental wounds, GM-CSF inhibited collagen deposition, possibly through prolonged monocyte infiltration (19). In the present study, romurtide induced peripheral monocytosis, MCP-1 upregulation, and ED-1-positive macrophage infiltration, suggesting excessive inflammation in local infarcted sites.…”

Platelet-Rich Fibrin Versus Albumin in Surgical Wound Repair

“…Studies in TGF-␤1-deficient mice suggest that endogenous TGF-␤1 increases inflammation 39 and elevated levels may then actually be detrimental. 19 Furthermore, raised TGF-␤1 alters receptor expression favoring a nonfibrotic response. 40 It should be emphasized that our measurements did not distinguish between TGF-␤1 derived from PRF or from TGF-␤1 induced indirectly by PRF.…”

“…8 Hydroxyproline was undetectable in PRF analyzed by high-performance liquid chromatography. 19 Human albumin (ZLB Bioplasma, Bern, Switzerland) was used as control at a final concentration of 14.2 g/L. This concentration matches that of PRF 8 and lacks growth-promoting activity on cultured fibroblasts.…”

The Effect of Preoperative Radiotherapy on Systemic Collagen Deposition and Postoperative Infective Complications in Rectal Cancer Patients

“…In this study, the subcutaneous tissue repair model measures the connective tissue response to acute radiation injury assessed indirectly as deposition of collagen relative to total protein. 19 The hydroxyproline is generally present as mature collagen (hydroxylation of proline in the procollagen molecules results in the formation of the triple helical mature collagen molecule specially rich in hydroxyproline), whereas proline is an accurate measure of the deposition of total protein. Radiotherapy depressed deposition of hydroxyproline in ePTFE tubes in mastectomy scars compared with control mastectomy scars.…”