PMID- 34201546
OWN - NLM
STAT- MEDLINE
DCOM- 20210803
LR  - 20210803
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 13
DP  - 2021 Jun 23
TI  - Ultra-Low Dose Cytokines in Rheumatoid Arthritis, Three Birds with One Stone as 
      the Rationale of the 2LARTH((R)) Micro-Immunotherapy Treatment.
LID - 10.3390/ijms22136717 [doi]
LID - 6717
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are two cytokines 
      involved in the perpetuation of the chronic inflammation state characterizing 
      rheumatoid arthritis (RA). Significant advances in the treatment of this 
      pathology have been made over the past ten years, partially through the 
      development of anti-TNF and anti-IL-1 therapies. However, major side effects 
      still persist and new alternative therapies should be considered. The formulation 
      of the micro-immunotherapy medicine (MIM) 2LARTH((R)) uses ultra-low doses (ULD) of 
      TNF-alpha, IL-1beta, and IL-2, in association with other immune factors, to gently 
      restore the body's homeostasis. The first part of this review aims at delineating 
      the pivotal roles played by IL-1beta and TNF-alpha in RA physiopathology, leading to the 
      development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an 
      emphasis will be made on explaining the rationale of using multiple therapeutic 
      targets, including both IL-1beta and TNF-alpha in 2LARTH((R)) medicine. Particular 
      attention will be paid to the ULD of those two main pro-inflammatory factors in 
      order to counteract their overexpression through the lens of their molecular 
      implication in RA pathogenesis.
FAU - Jacques, Camille
AU  - Jacques C
AD  - Preclinical Research Department, Labo'Life France, 1 Rue Francois Bruneau, 44000 
      Nantes, France.
FAU - Floris, Ilaria
AU  - Floris I
AUID- ORCID: 0000-0003-4089-3133
AD  - Preclinical Research Department, Labo'Life France, 1 Rue Francois Bruneau, 44000 
      Nantes, France.
FAU - Lejeune, Beatrice
AU  - Lejeune B
AD  - Preclinical Research Department, Labo'Life France, 1 Rue Francois Bruneau, 44000 
      Nantes, France.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210623
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Cytokines)
RN  - 0 (IL1B protein, human)
RN  - 0 (IL2 protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-2)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Arthritis, Rheumatoid/*drug therapy/physiopathology
MH  - Cytokines/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Interleukin-1beta/*administration & dosage/adverse effects/antagonists & 
      inhibitors/physiology
MH  - Interleukin-2/administration & dosage/adverse effects
MH  - Molecular Targeted Therapy/methods
MH  - Precision Medicine
MH  - Tumor Necrosis Factor-alpha/*administration & dosage/adverse effects/antagonists 
      & inhibitors/physiology
PMC - PMC8268272
OTO - NOTNLM
OT  - IL-1beta
OT  - TNF-alpha
OT  - anti-inflammatory medicines
OT  - chronic inflammation
OT  - hormesis
OT  - inflammatory cytokines
OT  - micro-immunotherapy
OT  - rheumatoid arthritis
OT  - ultra-low doses
COIS- The authors declare the following potential conflicts of interest with respect to 
      the research, authorship, and/or publication of this article: C.J., I.F. and B.L. 
      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.
EDAT- 2021/07/03 06:00
MHDA- 2021/08/04 06:00
PMCR- 2021/06/23
CRDT- 2021/07/02 01:11
PHST- 2021/05/20 00:00 [received]
PHST- 2021/06/15 00:00 [revised]
PHST- 2021/06/20 00:00 [accepted]
PHST- 2021/07/02 01:11 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/08/04 06:00 [medline]
PHST- 2021/06/23 00:00 [pmc-release]
AID - ijms22136717 [pii]
AID - ijms-22-06717 [pii]
AID - 10.3390/ijms22136717 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jun 23;22(13):6717. doi: 10.3390/ijms22136717.