LPS-Induced TNF-α and IL-1 Signaling in Periodontitis: Molecular Mechanisms and Therapeutic Opportunities

Periodontitis is a chronic, dysbiosis-driven inflammatory disease, that, unlike gingivitis, results in irreversible, tooth-supporting soft tissue and bone loss. Clarifying the molecular pathways that sustain the host inflammatory response is therefore central to improving disease management. Lipopolysaccharide (LPS), a major pathogen-associated molecular pattern of Gram-negative bacteria, is one important—though not the sole—microbial stimulus that drives inflammation in the polymicrobial, dysbiotic periodontal environment. This narrative review summarizes how LPS-initiated signaling promotes production of the pro-inflammatory cytokines TNF-α and IL-1, how these cytokines couple inflammation to osteoclast-mediated bone loss, and whether their pharmacological blockade holds therapeutic promise. A literature search combining the terms “LPS,” “periodontitis,” “TNF-α,” and “IL-1” was conducted in PubMed/MEDLINE, Scopus, and Google Scholar for English-language articles published up to 2026, with priority given to primary studies over secondary citations. Preclinical models consistently show that TNF-α and IL-1 blockade reduces periodontal inflammation and bone loss, but the effect is time-dependent: short-term blockade can aid healing whereas prolonged blockade may impair it, and robust periodontitis-specific clinical trials are lacking. We conclude that targeted modulation of TNF-α and IL-1—particularly through locally delivered, appropriately timed agents used as an adjunct to conventional mechanical therapy—is a biologically rational strategy.