Combined Lactoferrin and Osteopontin Treatment Attenuates LPS-Induced Inflammatory Responses and Intestinal Injury in Macrophages and Mice

This study explored the combined anti-inflammatory potential of lactoferrin (LF) and osteopontin (OPN) using both in vitro (LPS-challenged macrophages) and in vivo (LPS-induced intestinal injury) models. The LF-OPN combination demonstrated superior efficacy over monotherapies in suppressing pro-inflammatory mediator expression in macrophages. In vivo, co-administration markedly attenuated intestinal-barrier disruption and preserved mucosal architecture, evidenced by increased villus height, crypt depth, and goblet-cell counts, surpassing the effects of OPN alone. This structural protection was accompanied by significant immunomodulation; the combination treatment elevated systemic and local anti-inflammatory cytokines while reducing pro-inflammatory ones more effectively than either single protein. Notably, at LF:OPN ratios of 1:1, 5:1, and 10:1, murine intestinal Il10 concentrations rose by 44.25%, 54.46%, and 60.02%, respectively, relative to LF group; Tnfα concentrations fell by 33.73%, 52.27%, and 37.80% at the same three ratios when benchmarked against the OPN group (all p < 0.05). These data reveal a potent combined effect of LF and OPN against acute inflammatory insults, suggesting a promising therapeutic combined effect. Future work should focus on elucidating the underlying signaling mechanisms and evaluating efficacy in chronic disease models.