Objective To investigate the causal relationship between 91 circulating inflammatory proteins and respiratory tract infection by bidirectional Mendelian randomization. Methods single nucleotide polymorphisms (SNPs) for 91 inflammatory circulating proteins were derived from GWAS data from a genome-wide association study of 14 824 subjects of European ancestry on the Olink Target platform, and SNPs for acute bronchitis, acute bronchiolitis, and acute laryngitis and tracheitis were derived from GWAS pooled data in the FinnGen database. Inverse variance weighting method was used as the main research method to conduct bidirectional Mendelian randomization analysis, and Cochran’ IVW Q test, MR-Egger regression method and one by one elimination method were used to conduct sensitivity tests to evaluate heterogeneity and horizontal pleiotropy. In order to reduce the incidence of Class I errors and improve the feasibility of the study, Bonferroni correction was performed.ResultsLevels of C hemokine C-X-C motif ligand 6 (CXCL6), matrix metalloproteinase-1 (MMP-1), hepatocyte growth factor (HGF), interleukin-10 (IL-10), chemokine C-X3-C motif ligand 1 (CX3CL1), and TNF-related activation-induced cytokine (TRANCE) were causally associated with acute bronchitis. MMP-1 level [OR: 1.239 0, 95%CI: 1.111 6-1.382 2, P<0.000 5] had a significant causal relationship with acute bronchitiss and played a promoting role. Levels of macrophage inflammatory protein-1α (MIP-1α), signaling lymphocyte activating molecules, and FMS-associated tyrosine kinase 3 ligand (FIt3L) were potentially causally associated with acute bronchiolitis. There was a potential causal relationship between C-X-C motif chemokine 5 (CXCL5), T cell surface glycoprotein CD6 subtype (CD6), fibroblast growth factor 19 (FGF-19), C-C motif chemokine 23 (CCL23), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor ligand superfamily member 12 (TNFSF12) levels and acute laryngitis and tracheitis. In reverse Mendelian randomization analysis, there were no positive results between acute bronchitis, acute bronchiolitis and 91 inflammatory factors. Acute laryngitis and tracheitis [OR: 1.076 3,95%CI: 1.012 9-1.143 7, P=0.017 6] were potentially causally associated with FGF-19 levels. Conclusions MMP-1 level have a significant causal relationship with acute bronchitis. The levels of other inflammatory factors such as CXCL6, HGF, MIP-1 alpha, FIt3L, CXCL5, FGF-19 are potentially causally associated with respiratory tract infections. MMP-1 may be an important target for the prediction or treatment of acute bronchitis.