Thymosin Beta-4 Resolves Eye Infection Inflammation by Activating Pro-Resolving Lipid Mediator Pathways

Thymosin beta-4 resolves bacterial keratitis inflammation by activating 5-LOX and 12/15-LOX enzymes, generating specialized pro-resolving mediators (lipoxins, resolvins), and directly enhancing macrophage phagocytosis through SPM pathway activation.

In vivo Pseudomonas aeruginosa-induced bacterial keratitis mouse model treated with adjunctive Tβ4. Assessed LOX enzyme expression, SPM end products (lipoxins, resolvins), and SPM receptor levels in corneal tissue. In vitro validation using LPS-stimulated RAW 264.7 macrophages with siRNA knockdown of Tβ4 and LOX enzymes. Tested phagocytosis and efferocytosis mechanisms.

Bacterial keratitis can cause blindness, and current treatments (antibiotics alone) don't address the inflammatory corneal damage. Tβ4 is the first peptide shown to activate natural resolution pathways in the eye, offering a mechanistic rationale for combining it with antibiotics to not only clear infection but actively promote healing and prevent vision loss.

This study reveals that Tβ4 works by activating the body's own inflammation-resolving machinery — not by suppressing inflammation but by promoting its natural resolution through SPMs. This is a paradigm shift from anti-inflammatory treatment (which can impair infection clearance) to pro-resolving treatment (which can resolve inflammation while maintaining host defense). The implications extend beyond keratitis to other inflammatory conditions.

Mouse corneal infection model — human keratitis may involve additional pathogens and inflammatory mechanisms. Only Pseudomonas aeruginosa tested — response to other keratitis-causing bacteria unknown. The distinction between direct (phagocytosis) and indirect (efferocytosis) SPM-mediated effects needs further clarification. Clinical translation requires human corneal studies.