Abstract
Transferon® is a complex drug based on a mixture of low molecular weight peptides. This biotherapeutic is employed as a coadjuvant in clinical trials of several diseases, including viral infections and allergies. Given that macrophages play key roles in pathogen recognition, phagocytosis, processing, and antigen presentation, we evaluated the effect of Transferon® on phenotype and function of macrophage-like cells derived from THP-1 monocytes. We determined the surface expression of CD80 and CD86 by flow cytometry and IL-1β, TNF-α, and IL-6 levels by ELISA. Transferon® alone did not alter the steady state of PMA-differentiated macrophage-like THP-1 cells. On the contrary, simultaneous stimulation of cells with Transferon® and LPS elicited a significant increase in CD80 (P ≤ 0.001) and CD86 (P ≤ 0.001) expression, as well as in IL-6 production (P ≤ 0.05) compared to the LPS control. CD80 expression and IL-6 production exhibited a positive correlation (r = 0.6, P ≤ 0.05) in cells exposed to Transferon® and LPS. Our results suggest that the administration of Transferon® induces the expression of costimulatory molecules and the secretion of cytokines in LPS-activated macrophages. Further studies are necessary to determine the implication of these findings in the therapeutic properties of Transferon®.
Highlights
Transferon® is a human dialyzable leucocyte extract (DLE), and its active pharmaceutical ingredient is a complex mixture of low molecular weight peptides with immunomodulatory properties
The mononuclear phagocytic system, which involves the differentiation of hematopoietic cells into blood monocytes and tissue macrophages, is an essential part of the innate immune system [12] since it performs several key functions, including phagocytosis, production of cell-activating cytokines, tissue remodeling, antigen presenting through MHCII, and expression of costimulatory molecules
During infections, macrophages can be activated by pathogen components, such as lipopolysaccharide (LPS) from Gram-negative bacteria, which is recognized by Toll-like receptor 4 (TLR-4) [14]
Summary
Transferon® is a human dialyzable leucocyte extract (DLE), and its active pharmaceutical ingredient is a complex mixture of low molecular weight peptides with immunomodulatory properties. DLEs activate TLR signaling in monocytes [8], NF-κB and cAMP in endothelial cells, and Journal of Immunology Research modify cytokine production in candida and herpes infection [3, 9] Another dialyzable leukocyte extracts, such as bovine source (bDLEs), decrease nitric oxide and TNF-α production in LPS-stimulated murine peritoneal macrophages [10] and induce macrophage differentiation to M2 alternative profile [11]. The mononuclear phagocytic system, which involves the differentiation of hematopoietic cells into blood monocytes and tissue macrophages, is an essential part of the innate immune system [12] since it performs several key functions, including phagocytosis, production of cell-activating cytokines, tissue remodeling, antigen presenting through MHCII, and expression of costimulatory molecules. Macrophages enhance their cytokine production and antigen-presenting cell (APC) capabilities [15]
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