Identifying a vascoconstrictor role for interleukin-6, a pro-inflammatory cytokine.

Abstract

Increased plasma levels of interleukin-6 (IL-6) have been associated with elevated blood pressure and is predicative of risk for a firSt myocardial infarction. We therefore hypothesized that interleukin-6 has vasoconstrictive properties. Methods for this study included quantification of tissue levels of IL-6 , by capture ELISA from angiotensin 11- . I i hypertensivie male, C57BL/6J mice. Ti~sue coJcentratioti of IL-6 was compared to con~rol normotensiv¢ samples (thoracic aortic segments). ·Blood pressure was monitored by telemetry and the direct effect of IL-6 on v.ascu~ar contractility was studied in thoracic aortas isolated from normotensive mice. Our results show that IL-6 was significantly elevated (231.4 pg/mg ± 13.4 pg/mg . . ~ . . . SEM) in angiotensin II-hypertensiye mice compared to controls (129.9 pg/mg ± 11.2 · pg/mg SEM) and WT mice displayed a higher increase in MAP to angiotensin 11-infusion (60.35 mmHg ± 4.55 mmHg) at the end of infusion period compared to IL-6 KO mice (33.81 mmHg ± 6.67 mmHg). Pre-treatment of denuded aortic rings from normotensive mice with IL-6 for 24 hours caused a significant inhibition of their contractile response to phenylephrine and endothelin-1. In contrast, there was no significant effect on relaxation response to sodium niroprusside. In endothelium intact aortic rings, IL-6 caused contraction in the presence of L-NAME to inhibit nitric oxide synthase. We conclude that depending upon the experimental conditions, IL-6 has vasoconstrictive properties.