The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

mRNA 疫苗对患有慢性炎症性疾病（包括心肌炎、类风湿性关节炎 (RA) 和炎症性肠病 (IBD)）的个体的影响尚不清楚。我们研究了 mRNA 疫苗在植入 LPS 泵的慢性炎症小鼠模型中的效果，重点关注毒性和免疫原性。在慢性炎症下，mRNA疫苗加剧了心脏损伤和心肌炎，诱发轻度心脏炎症，促炎细胞因子的产生增加，心脏中炎症细胞浸润增加。与此同时，出现了严重的肌肉损伤，线粒体融合和裂变因子受到干扰，发出肌肉修复受损的信号。然而，慢性炎症不会对疫苗接种部位的肌肉或体液免疫反应产生不利影响；然而，它部分降低了细胞介导的免疫反应，特别是 T 细胞的激活。这些发现强调了解决慢性炎症背景下 mRNA 疫苗毒性和免疫原性的重要性，确保其安全有效的利用，特别是在患有免疫介导的炎症性疾病的弱势群体中。