PMID- 30464572
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220330
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 11
DP  - 2018
TI  - 2LARTH((R)), a micro-immunotherapy medicine, exerts anti-inflammatory effects in 
      vitro and reduces TNF-alpha and IL-1beta secretion.
PG  - 397-405
LID - 10.2147/JIR.S174326 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and IL-1beta 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((R)) 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-alpha and IL-1beta 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((R)) for 
      24 hours. IL-1beta, TNF-alpha, and IL-6 release were evaluated by ELISA. RESULTS: The 
      medicine has significantly decreased the level of IL-1beta 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-alpha 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.
FAU - Floris, Ilaria
AU  - Floris I
AD  - Clinical Affairs, Labo'Life France, Moutiers-Sous-Chantemerle, France, 
      ilaria.floris@labolife.com.
FAU - Appel, Kurt
AU  - Appel K
AD  - VivaCell Biotechnology GmbH, Denzlingen, Germany.
FAU - Rose, Thorsten
AU  - Rose T
AD  - VivaCell Biotechnology GmbH, Denzlingen, Germany.
FAU - Lejeune, Beatrice
AU  - Lejeune B
AD  - Clinical Affairs, Labo'Life Belgium, Gembloux, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20181029
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC6211308
OTO - NOTNLM
OT  - chronic inflammation
OT  - hormesis
OT  - rheumatic diseases
OT  - ultra-low doses
COIS- Disclosure IF works for Labo'Life France, the company service provider for 
      Labo'Life, specializing in preclinical, clinical, and regulatory affairs. BL is 
      employed by Labo'Life Belgium, the pharmaceutical company that commercializes the 
      micro-immunotherapy medicine tested in the study. IF and BL declare that their 
      professional relationships with Labo'Life France and Labo'Life Belgium do not 
      imply any misconduct in this study. KA and TR work for VivaCell Biotechnology 
      GmbH, a contract research organization that specializes in preclinical research. 
      The authors report no other conflicts of interest in this work.
EDAT- 2018/11/23 06:00
MHDA- 2018/11/23 06:01
PMCR- 2018/10/29
CRDT- 2018/11/23 06:00
PHST- 2018/11/23 06:00 [entrez]
PHST- 2018/11/23 06:00 [pubmed]
PHST- 2018/11/23 06:01 [medline]
PHST- 2018/10/29 00:00 [pmc-release]
AID - jir-11-397 [pii]
AID - 10.2147/JIR.S174326 [doi]
PST - epublish
SO  - J Inflamm Res. 2018 Oct 29;11:397-405. doi: 10.2147/JIR.S174326. eCollection 
      2018.