Abstract
Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) 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® uses ultra-low doses (ULD) of TNF-α, IL-1β, 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-1β and TNF-α 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-1β and TNF-α in 2LARTH® 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.
Highlights
Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA)
TNF-α is a major factor of RA development within the synovial niche, as human synovial fibroblasts cultured in presence of TNF-α display increased expression of IL-1β, monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein-1 alpha (MIP1α), MMP-1, MMP-3 and receptor activator of nuclear factor-κB ligand (RANKL), an osteoclastogenic cytokine, compared to control cells [25]
MM, were compared with the vehicle-impregnated ones. These results were confirmed in PMA-differentiated THP-1 cells. These anti-inflammatory effects induced by ultra-low doses (ULD) of one cytokine at a time might be explained by the fact that IL-1β and TNF-α are strongly linked by an autocrine positive loop in monocytes after LPS exposure [89]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. TNF-α is a major factor of RA development within the synovial niche, as human synovial fibroblasts cultured in presence of TNF-α display increased expression of IL-1β, monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein-1 alpha (MIP1α), MMP-1, MMP-3 and receptor activator of nuclear factor-κB ligand (RANKL), an osteoclastogenic cytokine, compared to control cells [25]. In line with these results, TNF-α induces osteoclast differentiation in macrophages isolated from mouse bone marrow. The TNF receptor-associated factor 1 (TRAF1) and complement component 5 (C5) is known to act as a scaffold protein complex and play a direct role in the downstream TNF-α signaling, further reinforcing the link between the TNF-α pathway and the immune escape associated with RA outcome and comorbidities
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
