Kathamuthu Gokul Raj, Bhavani Perumal Kannabiran, Singh Manjula, Saini Jitendra Kumar, Aggarwal Ashutosh, Ansari Mohammed Soheb S, Garg Rajiv, Babu Subash
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
National Institute for Research in Tuberculosis (NIRT), Chennai, India.
Front Pharmacol. 2022 Jul 15;13:896551. doi: 10.3389/fphar.2022.896551. eCollection 2022.
High-dose rifampicin (HDR) is now undergoing clinical trials to improve the efficacy of anti-tuberculosis treatment (ATT). However, the influence of HDR in the modulation of different cytokines, chemokines/growth factors, microbial translocation markers (MTMs), and acute-phase proteins (APPs) in pulmonary tuberculosis (PTB) is not well known. PTB individuals were separated into three different arms (R10, R25, and R35) based on their rifampicin dosage. We examined the circulating levels of Type 1, Type 2, pro-inflammatory/regulatory cytokines, chemokines/growth factors, MTMs, and APPs at baseline and after completion of the second month of ATT by ELISA. The baseline levels of cytokines, chemokines/growth factors, MTMs, and APPs did not (except IL-5, IL-6, IL-17A, MCP-1, MIP-1β, GCSF, SAA, ⍺2 MG, Hp) significantly differ between the study individuals. However, at the second month, the plasma levels of Type 1 (TNFα and IFNγ), Type 2 (IL-4, IL-5, and IL-13), pro-inflammatory/regulatory cytokines (IL-6, IL-17A, IL-10, and GMCSF), and APPs were significantly decreased in R35 regimen- compared to R25 and/or R10 regimen-treated PTB individuals. In contrast, the plasma levels of IL-2, IL-8, MCP-1, MIP-1β, GSF, and MTMs were significantly increased in the R35 regimen compared to R25 and/or R10 regimen-treated PTB individuals. Overall, our data reveal that HDR could potentially be beneficial for host immunity by altering different immune and inflammatory markers.
高剂量利福平(HDR)目前正在进行临床试验,以提高抗结核治疗(ATT)的疗效。然而,HDR对肺结核(PTB)中不同细胞因子、趋化因子/生长因子、微生物易位标志物(MTMs)和急性期蛋白(APPs)的调节作用尚不清楚。根据利福平剂量,将PTB患者分为三个不同组(R10、R25和R35)。我们通过酶联免疫吸附测定法(ELISA)检测了ATT第二个月结束时和基线时1型、2型、促炎/调节性细胞因子、趋化因子/生长因子、MTMs和APPs的循环水平。细胞因子、趋化因子/生长因子、MTMs和APPs的基线水平在研究个体之间没有显著差异(白细胞介素-5、白细胞介素-6、白细胞介素-17A、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1β、粒细胞集落刺激因子、血清淀粉样蛋白A、α2微球蛋白、结合珠蛋白除外)。然而,在第二个月时,与接受R25和/或R10方案治疗的PTB患者相比,R35方案治疗的PTB患者血浆中1型(肿瘤坏死因子α和干扰素γ)、2型(白细胞介素-4、白细胞介素-5和白细胞介素-13)、促炎/调节性细胞因子(白细胞介素-6、白细胞介素-17A、白细胞介素-10和粒细胞-巨噬细胞集落刺激因子)和APPs水平显著降低。相反,与接受R25和/或R10方案治疗的PTB患者相比,R35方案治疗的PTB患者血浆中白细胞介素-2、白细胞介素-8、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1β、粒细胞集落刺激因子和MTMs水平显著升高。总体而言,我们的数据表明,HDR可能通过改变不同的免疫和炎症标志物对宿主免疫有益。