Anti-inflammatory and immunomodulatory properties of fosfomycin: an overlooked potential in a well-known antibiotic.

Fosfomycin, a broad-spectrum bactericidal antibiotic, has recently gained interest for its potential anti-inflammatory and immunomodulatory effects beyond its well-established antimicrobial activity. Emerging evidence from preclinical studies demonstrates that fosfomycin suppresses key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, while enhancing anti-inflammatory mediators such as IL-10. It modulates essential intracellular pathways by inhibiting NF-κB and MAPK signaling and reducing NLRP3 inflammasome activation. Fosfomycin also influences immune cell function by limiting neutrophil migration and activation, suppressing T-cell proliferation, and decreasing B-cell immunoglobulin production. In addition, it promotes tissue regeneration through enhanced collagen deposition, angiogenesis, and improved wound healing in experimental models. These combined effects suggest a dual therapeutic role for fosfomycin, both in controlling infection and modulating inflammatory responses. Despite promising preclinical results, clinical evidence on its immunomodulatory effects remains limited, with most human studies primarily addressing its antibacterial efficacy. This review summarizes current knowledge on fosfomycin's non-antibacterial properties, highlights its therapeutic potential in inflammatory and infectious diseases, and identifies research gaps that warrant further investigation. Overall, fosfomycin emerges as a promising adjunctive agent, particularly in conditions such as sepsis, chronic wounds, and sterile surgical inflammation, where excessive immune activation impairs recovery.