Special Focus on the Cellular Anti-Inflammatory Effects of Several Micro-Immunotherapy Formulations: Considerations Regarding Intestinal-, Immune-Axis-Related- and Neuronal-Inflammation Contexts.

Introduction: Chronic inflammation is a pernicious underlying status, well-known for its contribution to the progressive development of various diseases. In this regard, Micro-immunotherapy (MI) might be a promising therapeutic strategy. MI employs low doses (LD) and ultra-low doses (ULD) of immune regulators in their formulations. In particular, as both IL-1β and TNF-α are often used at ULD in MI medicines (MIM), a special emphasis has been made on formulations that include these factors in their compositions. Methods: Several in vitro models have been employed in order to assess the effects of two unitary MIM consisting of ULD of IL-1β and TNF-α (u-MIM-1 and u-MIM-2, respectively), and four complex MIM (c-MIM-1, -2, -3 and -4) characterized by the presence of ULD of IL-1β and TNF-α amongst other factors. Thus, we first investigated the anti-inflammatory effects of u-MIM-1 and u-MIM-2 in a model of inflamed colon carcinoma cells. In addition, the anti-inflammatory potential of c-MIM-1, -2, -3 and -4, was assessed in in vitro models of intestinal and neuronal inflammation. Results: The results revealed that u-MIM-1 and u-MIM-2 both induced a slight decrease in the levels of IL-1β and TNF-α transcripts. Regarding the c-MIMs' effects, c-MIM-1 displayed the capability to restore the altered transepithelial electrical resistance in inflamed-HCoEpiC cells. Moreover, c-MIM-1 also slightly increased the expression of the junction-related protein claudin-1, both at the mRNA and protein levels. In addition, our in vitro investigations on c-MIM-2 and c-MIM-3 revealed their immune-modulatory effects in LPS-inflamed human monocytes, macrophages, and granulocytes, on the secretion of cytokines such as TNF-α, PGE2, and IL-6. Finally, c-MIM-4 restored the cell viability of LPS/IFN-γ-inflamed rat cortical neurons, while reducing the secretion of TNF-α in rat glial cells. Discussion: Our results shed the light on the potential role of these MIM formulations in managing several chronic inflammation-related conditions.