Interleukin-10 inhibits human vascular smooth muscle proliferation.
Arterial injury results in the elaboration of pro-inflammatory substances including cytokines and peptide growth factors which act to modify vascular smooth muscle (VSMC) proliferation and migration with resultant vessel stenosis. Produced by T-lymphocytes and macrophages, interleukin-10 (IL-10) is an anti-inflammatory cytokine in several cell lines. We hypothesized that IL-10 may participate in vascular remodeling by inhibiting VSMC proliferation. Human aortic VSMCs were isolated and cultured. Proliferation assays were performed to determine the effect of the effect of IL-10 on (1) unstimulated, (2) cytokine (tumor necrosis factor-alpha: TNF alpha)-stimulated, and (3) growth factor (basic fibroblast growth factor: bFGF)-stimulated VSMC proliferation. Compared to control, both TNF alpha and bFGF-stimulated VSMC proliferation (P < 0.002). IL-10 alone had no effect on cell growth. However, with TNF alpha or bFGF-stimulation, physiologic doses of IL-10 inhibited both VSMC DNA synthesis and VSMC growth (P < 0.001). Furthermore, IL-10 was effective in inhibiting TNF alpha-induced proliferation at a dose as low as 10 fg/ml (P < 0.001) and bFGF-induced proliferation at a dose as low as 1 pg/ml (P < 0.001). In conclusion, TNF alpha and bFGF stimulate human VSMC growth. IL-10 potently abrogates the proliferative response to these atherogenic mitogens. IL-10 might represent an endogenous source of immune-mediated atherprotection and when given exogenously, may prove to be a novel therapeutic agent in regulating vessel wall remodeling following vascular injury.
Selzman
C H
CH
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
McIntyre
R C
RC
Shames
B D
BD
Whitehill
T A
TA
Banerjee
A
A
Harken
A H
AH
D001011:Aorta; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D016753:Interleukin-10