How an Immune-Factor-Based Formulation of Micro-Immunotherapy Could Interfere with the Physiological Processes Involved in the Atopic March

Abstract

Allergic diseases consist of improper inflammatory reactions to antigens and are currently an important healthcare concern, especially considering their increasing worldwide development in recent decades. The “atopic march” defines the paradigm of allergic diseases occurring in chronological order and displaying specific spatial manifestations, as they usually start as atopic dermatitis (AD) and food allergies during infancy and progressively evolve into allergic asthma (AA) and allergic rhinitis (AR) or rhino-conjunctivitis in childhood. Many immune cell subtypes and inflammatory factors are involved in these hypersensitivity reactions. In particular, the T helpers 2 (Th2) subset, through its cytokine signatures made of interleukins (ILs), such as IL-4, IL-5, IL-10, and IL-13, as well as mast cells and their related histamine pathways, contribute greatly to the perpetuation and evolution of the atopic march. By providing low doses (LD) and ultra-low doses (ULD) of ILs and immune factors to the body, micro-immunotherapy (MI) constitutes an interesting therapeutic strategy for the management of the atopic march and its symptoms. One of the aims of this review is to shed light on the current concept of the atopic march and the underlying immune reactions occurring during the IgE-mediated responses. Moreover, the different classes of traditional and innovative treatments employed in allergic diseases will also be discussed, with a special emphasis on the potential benefits of the MI medicine 2LALERG® formulation in this context.

In Vitro Study of Interleukin-6 when Used at Low Dose and Ultra-Low Dose in Micro-Immunotherapy

“…Indeed, the tested capsule of this medicine seemed to reduce the release of IL-6 itself in lipopolysaccharide (LPS)-inflamed human macrophages, and it also inhibited the histamine degranulation of rats’ peritoneal mast cells. These additional data, even if they still need to be completed, definitely contribute to adding more information about ULD-IL-6 when employed in MI, thus strengthening the current knowledge about the mode of action of 2LALERG ® , previously reported in an in vivo model of allergic disease [ 28 , 33 ]. To conclude, the overall study, by addressing both sides of the LD/ultra-low dose (ULD) ranges used in MI, provided novel pieces of evidence on their double-edged potential in modulating the immune responses.…”

“…Moreover, the evidence of an IL-6-mediated-autocrine growth loop was then confirmed in the human myeloma cells U266 [ 64 ]. Nonetheless, while these first results were solely collected from in vitro experiments, previous in vivo results with the 2LALERG ® therapy were also able to highlight its systemic effects in reducing pro-inflammatory markers such as IL-4 and IL-5, the latter being employed at ULD in the complete formulation of 2LALERG ® [ 28 , 33 ]. Furthermore, as the pharmacological inhibition of IL-6 together with TNF has been suggested to be beneficial for patients suffering from severe allergic asthma [ 65 ], it is also interesting to mention that the complete formulation of 2LALERG ® also encompasses ULD of TNF-α.…”

“…Finally, as histamine is a well-known mediator of allergic reactions, the capacity of IL-6 to stimulate mast cells’ histamine degranulation has been documented, and it is even one of the pillars of the rationale for the employment of this cytokine at ULD in the formulation of the MIM 2LALERG ® [ 33 ]. The final part of the current study thus aimed at assessing the effect of the tested 2LALERG ® capsule on the histamine degranulation of rat mast cells.…”

“…In particular, one of these studies pointed to the in vivo effects of the complete sequential administration of the complex-MIM 2LALERG ® , which contains IL-6 at 17 CH, in reducing the inflammation of the lungs as well as the circulating levels of some T helper cell type 2 (Th2)-related cytokines and immunoglobulin (Ig) E in a mice model of birch pollen-induced allergic inflammation [ 28 ]. Furthermore, the rationale behind the IL-6-inhibition strategy through MI, within the context of the atopic march process, has also been previously discussed [ 33 ]. In line with this body of literature, the current manuscript is thus also interested in advancing on the preclinical research about the IL-6-ULD-containing MIM 2LALERG ® .…”

Actives from the Micro-Immunotherapy Medicine 2LMIREG® Reduce the Expression of Cytokines and Immune-Related Markers Including Interleukin-2 and HLA-II While Modulating Oxidative Stress and Mitochondrial Function

“…As our previous publications reported that the ULD employed in MI displayed inhibitory effects, 9–14 , 26 , 27 these data provided us a rationale for the selection of the MIM capsules which encompass ULD of IL-1β, IL-2, TGF-β, and TNF-α, either alone or combined together, in order to further test their abilities to reduce the mitochondrial-ROS production.…”