To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, β = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, β = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, β = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, β = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025–234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways.

使用孟德尔随机化 (MR) 方法检查循环白细胞介素 6 (IL-6) 水平 (CirIL6) 是否对血压有因果影响。我们使用欧洲血统全基因组关联研究 (GWAS) 的数据来获得用于循环 IL-6 水平和血压测量的遗传仪器。我们应用了几种稳健的 MR 方法来估计因果效应并测试异质性和多效性。我们发现循环IL-6对收缩压（SBP）和肺动脉高压（PAH）有显着的正因果作用，但对舒张压（DBP）或高血压没有显着的正因果作用。我们发现，使用逆方差加权（IVW）方法，随着 CirIL6 基因增加，SBP 增加（对于 ukb-b-20175，β = 0.082，SE = 0.032，P  = 0.011；对于 ukb-a-360，β = 0.075，SE = 0.031，P  = 0.014）和加权中位数（WM）法（对于 ukb-b-20175，β = 0.061，SE = 0.022，P  = 0.006；对于 ukb-a-360，β = 0.065，SE = 0.027，P  = 0.014）。此外，使用 WM 方法时，CirIL6 可能与 PAH 风险增加相关（比值比 (OR) = 15.503，95% CI，1.025–234.525，  P  = 0.048），但使用 IVW 方法时则不然。我们的研究提供了新的证据，证明循环中的 IL-6 在 SBP 和 PAH 的发生中具有因果作用，但与 DBP 或高血压无关。这些发现表明IL-6可能是预防或治疗心血管疾病和代谢紊乱的潜在治疗靶点。然而，需要更多的研究来证实 IL-6 对血压的因果影响并阐明潜在的机制和途径。