Dalhousie Human Immunology and Inflammation Group, Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, Room 7-C2, 5850 College Street, PO Box 15000, Halifax, NS, B3H 4R2, Canada.
Senescence, Aging, Infection and Immunity Laboratory, Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Sci Rep. 2021 Apr 30;11(1):9405. doi: 10.1038/s41598-021-88829-w.
Histamine receptor 2 (H2R) blockade is commonly used in patients with gastric, duodenal ulcers or gastroesophageal reflux disease. Beyond the gastrointestinal tract, H2R is expressed by multiple immune cells, yet little is known about the immunomodulatory effects of such treatment. Clinical reports have associated H2R blockade with leukopenia, neutropenia, and myelosuppression, and has been shown to provide clinical benefit in certain cancer settings. To systematically assess effects of H2R blockade on key immune parameters, a single-center, single-arm clinical study was conducted in 29 healthy subjects. Subjects received daily high dose ranitidine for 6 weeks. Peripheral blood immunophenotyping and mediator analysis were performed at baseline, 3 and 6 weeks into treatment, and 12 weeks after treatment cessation. Ranitidine was well-tolerated, and no drug related adverse events were observed. Ranitidine had no effect on number of neutrophils, basophils or eosinophils. However, ranitidine decreased numbers of B cells and IL-2Rα (CD25) expressing T cells that remained lower even after treatment cessation. Reduced serum levels of IL-2 were also observed and remained low after treatment. These observations highlight a previously unrecognised immunomodulatory sustained impact of H2R blockade. Therefore, the immune impacts of H2R blockade may require greater consideration in the context of vaccination and immunotherapy.
组胺受体 2（H2R）阻断剂常用于治疗胃、十二指肠溃疡或胃食管反流病患者。除了胃肠道，H2R 还在多种免疫细胞上表达，但其治疗的免疫调节作用知之甚少。临床报告显示，H2R 阻断剂与白细胞减少症、中性粒细胞减少症和骨髓抑制有关，并已在某些癌症治疗中显示出临床获益。为了系统评估 H2R 阻断剂对关键免疫参数的影响，在 29 名健康受试者中进行了一项单中心、单臂临床研究。受试者接受每日高剂量雷尼替丁治疗 6 周。在基线、治疗 3 周和 6 周以及治疗停止后 12 周时进行外周血免疫表型和介质分析。雷尼替丁耐受性良好，未观察到与药物相关的不良事件。雷尼替丁对中性粒细胞、嗜碱性粒细胞或嗜酸性粒细胞的数量没有影响。然而，雷尼替丁减少了 B 细胞和表达 IL-2Rα（CD25）的 T 细胞的数量，即使在治疗停止后，这些数量仍保持较低水平。还观察到血清 IL-2 水平降低，并且在治疗后仍保持较低水平。这些观察结果突出了 H2R 阻断剂以前未被认识到的持续免疫调节作用。因此，在疫苗接种和免疫治疗背景下，H2R 阻断剂的免疫影响可能需要更多的考虑。
