2LARTH(®), a micro-immunotherapy medicine, exerts anti-inflammatory effects in vitro and reduces TNF-α and IL-1β secretion

BACKGROUND: Tumor necrosis factor-α (TNF-α) and IL-1β are 2 pro-inflammatory cytokines known to be involved in rheumatic diseases. The therapeutic strategy used in micro-immunotherapy (MI) to reduce chronic inflammation and attenuate pain consists in mainly targeting these 2 cytokines. 2LARTH(®) is a sublingually administered medicine consisting of lactose-saccharose globules impregnated with ethanolic preparations of immune mediators and nucleic acids at ultra-low doses. PURPOSE: The aim of the study is to explore the effect of the MI medicine on TNF-α and IL-1β secretion in human primary enriched monocytes exposed to lipopolysaccharide (LPS). MATERIALS AND METHODS: Placebo and active globules were diluted in culture medium to test 5 lactose-saccharose globules concentrations (from 1.75 to 22 mM). Freshly isolated enriched monocytes from 6 healthy donors were treated with or without LPS (10 ng/mL), LPS+ placebo, or LPS+ 2LARTH(®) for 24 hours. IL-1β, TNF-α, and IL-6 release were evaluated by ELISA. RESULTS: The medicine has significantly decreased the level of IL-1β secretion compared with placebo at these concentrations: 22 mM (P<0.0001), 11 mM (P=0.0086), 5.5 mM (P= 0.0254), and compared with untreated LPS control at these concentrations: 22 mM, 11 mM (P=0.0008), and 5.5 mM (P=0.002). The effect of active globules on the reduction of TNF-α release is significant compared with placebo at these concentrations: 22 mM (P=0.0018), 11 mM (P=0.0005), 5.5 mM (P=0.0136), and compared with untreated LPS control at these concentrations: 22 mM (P=0.0021), 11 mM (P=0.0017), 5.5 mM (P=0.0052) and 2.25 mM (P=0.0196). Besides, IL-6 secretion decreased compared with placebo at 22 mM (P=0.0177) and 11 mM (P=0.0031). CONCLUSION: The results indicate that the tested product exerts significant anti-inflammatory effects on human LPS-stimulated monocytes.