Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control

Abstract

Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert a significant role in the survival, growth, and immune development of neonatal calves. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 (241.3 pg/mL) production induced by PMA (p < 0.05), while increasing IL-10 production (45.3 pg/mL), in comparison to PMA control (441.1 and 12.5 pg/mL, respectively). Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-κB activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration and intestinal score, and suppressed IL-6 (142.0 pg/mL) production during S. typhimurium infection, in comparison to control animals (215.2 pg/mL). These results suggest the immunomodulatory activity of bovine colostrum and its potential applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models.

Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study

“…In a study exploring the immunomodulatory properties of BC on cytokine production in vitro and in a novel murine-calf fecal microbiota transplantation model, the inhibition effect on IL-6 output and amplified IL-10 production was recorded. In the presence of S. typhimurium infection, colostrum exhibited reduced gut permeability, a decrease in immune cell penetration, and curtailed IL-6 production [36]. This emphasizes the potential of bovine colostrum in modulating the immune response and its potential therapeutic roles in addressing inflammatory conditions.…”

“…The compromised gut barrier can result in the translocation of bacteria and other antigens into the bloodstream, potentially leading to inflammation. BC might strengthen the gut's defense mechanisms [36][37][38].…”

A Comprehensive Review of Bovine Colostrum Components and Selected Aspects Regarding Their Impact on Neonatal Calf Physiology

“…Cytokines are essential in the immune response, but some cytokines need tight regulation; otherwise, the inflammatory process can have nefarious effects on the organism. For example, IL-6 plays important roles in inflammatory processes at the intestinal level but can also cause tissue damage, compromise the integrity of the intestinal barrier, and lead to systemic infections when overproduced [205,206]. IL-6 is mediated by the nuclear factor kB (NF-kB), which is involved in the pathogenesis of inflammatory diseases [207].…”

“…IL-6 is mediated by the nuclear factor kB (NF-kB), which is involved in the pathogenesis of inflammatory diseases [207]. Bovine colostrum was able to reduce NF-kB activation and, consequently, IL-6 production in an in vitro model [206]. In another in vitro model, colostrum inhibited the NF-kB pathway in human colon cancer HT29 cells, protecting against intestinal epithelial cell inflammation [208].…”