Effect of interleukin-6 and interleukin-10 on nitric oxide production by endothelial cells

Introduction

Nitric oxide (NO) is synthesised from conversion of L-arginine to citrulline by NO-synthase (NOS). NO mediates vascular dilation, muscle relaxation and platelet aggregation. Constitutive NOS (cNOS) exists in endothelial cells but not in vascular smooth muscle. Among others the cytokines IL-6 and IL-10 can be measured in high concentrations during sepsis. IL-10 has an inhibitory effect on the NO synthesis in LPS stimulated macrophages by inhibiting NOS. Recently, IL-10 have been reported to have a stimulatory effect on the NO production by endothelial cells in human saphenous veins in a concentration dependent way.

Aim

To investigate the in vitro effect of IL-10 and IL-6 on NO production by endothelial cells in human saphenous veins.

Methods

Human saphenous veins from patients undergoing CPB were used. The vessels were suspended in phosphate buffered saline (PBS) with the endothelial side up. The tip of the amperometic probe was positioned 10 μm above the cell surface. Concentrations of the NO gas in the PBS solution were measured in real time with a DUO 18 computer data acquisition.

Results

The vessels were exposed to IL-10 (10^-8 M), IL-6 (10^-6 M) anti-IL-6 (l0^-6 M) alone or in combination. IL-10 increased the NO production by the endothelial cells. IL-6 on its own did not affect the NO production. When IL-6 was added minutes following the IL-10 administration, it diminished the IL-10 induced NO release. Anti-IL-6 did not have any influence on the NO production, but the IL-6 inhibition of IL-10 stimulated NO release, was blocked when anti IL-6 was added.

Conclusion

These results show that IL-10 stimulate NO release from endothelial cells. Addition of IL-6 can attenuate the effect of IL-10 on endothelial cells.