PMID- 33633511 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210227 IS - 1559-3258 (Print) IS - 1559-3258 (Electronic) IS - 1559-3258 (Linking) VI - 18 IP - 4 DP - 2020 Oct-Dec TI - Pro-Inflammatory Cytokines at Ultra-Low Dose Exert Anti-Inflammatory Effect In Vitro: A Possible Mode of Action Involving Sub-Micron Particles? PG - 1559325820961723 LID - 10.1177/1559325820961723 [doi] LID - 1559325820961723 AB - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are pro-inflammatory cytokines involved in acute and chronic inflammatory diseases. Indeed, immunotherapy blocking these 2 cytokines has been developed. Micro-immunotherapy (MI) also uses ultra-low doses (ULD) of pro-inflammatory cytokines, impregnated on lactose-sucrose pillules, to counteract their overexpression. The study has been conducted with 2 objectives: examine the anti-inflammatory effect in vitro and the capacity of 2 unitary medicines, TNF-alpha (27 CH) and IL-1beta (27 CH), to reduce the secretion of TNF-alpha in human primary monocytes and THP-1 cells differentiated with phorbol-12-myristate-13-acetate, after lipopolysaccharide (LPS) exposure; then, investigate the presence of particles possibly containing starting materials using tunable resistive pulse sensing technique. The results show that the unitary medicines, tested at 3 pillules concentrations (5.5, 11 and 22 mM), have reduced the secretion of TNF-alpha in both models by about 10-20% vs. vehicle control, depending on concentration. In this exploratory study, particles (150-1000 nm) have been detected in MI ULD-impregnated pillules and a hypothesis for MI medicines mode of action has been proposed. Conscious that more evaluations are necessary, authors are cautious in the conclusions because the findings described in the study are still limited, and future investigations may lead to different hypothesis. CI - (c) The Author(s) 2020. FAU - Floris, Ilaria AU - Floris I AUID- ORCID: 0000-0003-4089-3133 AD - Preclinical Research, Clinical Research, Regulatory Affairs Departments, Labo'Life France, Nantes, France. FAU - Rose, Thorsten AU - Rose T AD - VivaCell Biotechnology GmbH, Denzlingen, Germany. FAU - Rojas, Juan Antonio Collado AU - Rojas JAC AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Cordoba, Spain. FAU - Appel, Kurt AU - Appel K AUID- ORCID: 0000-0002-4315-4478 AD - VivaCell Biotechnology GmbH, Denzlingen, Germany. FAU - Roesch, Camille AU - Roesch C AD - Izon Science Europe SAS, Lyon, France. FAU - Lejeune, Beatrice AU - Lejeune B AUID- ORCID: 0000-0001-9067-6116 AD - Preclinical Research, Clinical Research, Regulatory Affairs Departments, Labo'Life France, Nantes, France. LA - eng PT - Journal Article DEP - 20201021 PL - United States TA - Dose Response JT - Dose-response : a publication of International Hormesis Society JID - 101308899 PMC - PMC7829609 OTO - NOTNLM OT - anti-inflammatory unitary medicines OT - micro-immunotherapy OT - sub-micron particles OT - ultra-low doses COIS- Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: IF and BL work for Labo'Life France, the company service provider of Labo'Life, specialized in preclinical and clinical research, as well as regulatory affairs. This professional relationship does not imply any misconduct on the part of the authors. KA and TR work for Vivacell, Biotechnology GmbH, a biotechnological company specialized in preclinical research. JACR works in the Instituto Maimonides de Investigacion Biomedica of Cordoba. CR works for Izon Science Europe SAS. EDAT- 2021/02/27 06:00 MHDA- 2021/02/27 06:01 PMCR- 2020/10/21 CRDT- 2021/02/26 06:02 PHST- 2020/05/15 00:00 [received] PHST- 2020/08/26 00:00 [revised] PHST- 2020/08/31 00:00 [accepted] PHST- 2021/02/26 06:02 [entrez] PHST- 2021/02/27 06:00 [pubmed] PHST- 2021/02/27 06:01 [medline] PHST- 2020/10/21 00:00 [pmc-release] AID - 10.1177_1559325820961723 [pii] AID - 10.1177/1559325820961723 [doi] PST - epublish SO - Dose Response. 2020 Oct 21;18(4):1559325820961723. doi: 10.1177/1559325820961723. eCollection 2020 Oct-Dec.