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.

Keywords: Caco-2 cells; NF-κB; S. typhimurium infection; THP-1 macrophages; bovine colostrum; cytokine production; immunomodulation; inflammatory disorders; intestinal permeability.

Figure 1

Bovine colostrum exerts immunomodulatory and chemoprotective activity on the Caco-1/THP-1 macrophage co-culture system. Panel (A) shows the morphological changes of Caco-2, THP-1, and co-cultures during the stimulation with Phorbol 12-myristate 13-acetate (PMA) and treatment with bovine colostrum (COL). Scale bar represents 100 µm. Panel (B) shows the effects of bovine colostrum on PMA-induced cytokine production by Caco-2/THP-1 macrophage co-culture. Panel (C) shows the effects of bovine colostrum on PMA-induced LDH release and transepithelial electric resistance (TEER) changes. Panel (D) demonstrates the effect of various treatments of bovine colostrum on the ability to suppress IL-6 production by Caco-2/THP-1 cells. Data are shown as mean ± standard deviation (SD). ns—non-significant.

Figure 2

Bovine colostrum is able to reduce IL-6 production via THP-1-derived macrophage modulation. Panel (A) shows the effects of COL treatment on PMA-induced IL-6 production by Caco-2, THP-1 derived macrophages or their co-cultures. Panel (B) shows Western blots for NF-κB from THP-1-derived macrophages and Caco-2 co-culture. Data are shown as mean ± standard deviation (SD).

Figure 3

Bovine colostrum decreases intestinal permeability and infiltration with immune cells in calf-FMT C57BL/6 mice. Panel (A) demonstrates the intestinal permeability and inflammation measured by Evans blue assay. Panel (B) shows representative photomicrographs of the mouse intestine stained with hematoxylin/eosin (HE) and Alcian blue (AB). Panel (C) shows the pathological scoring of calf-FMT C57BL6 mice undergoing feeding with normal saline (NS) and colostrum (COL). Data are shown as mean ± standard deviation (SD).

Figure 4

Bovine colostrum reduces intestinal inflammation in calf-FMT C57BL/6 mice lethally challenged with S. typhimurium ATCC 14028 strain. Panel (A) demonstrates the intestinal permeability and inflammation measured by Evans blue assay followed by lethal challenge with S. typhimurium ATCC 14028. Panel (B) shows representative photomicrographs of S. typhimurium infected calf-FMT C57BL/6 mouse intestine stained with hematoxilin/eosin (HE) and Alcian blue (AB). Panel (C) shows the pathological scoring of Salmonella-infected calf-FMT C57BL6 mice undergoing feeding with normal saline (NS) and colostrum (COL). Data are shown as mean ± standard deviation (SD).

Figure 5

Bovine colostrum exhibits IL-6-targeted anti-inflammatory effects and mitigates S. typhimurium ATCC 14028 infection in calf-FMT C57BL/6 mice. Panel (A) illustrates cytokine production in calf-FMT C57BL/6 mice subjected to colostrum feeding. Panel (B) displays cytokine production in response to a lethal challenge with the S. typhimurium ATCC 14028 strain. Panel (C) presents survival data of calf-FMT C57BL/6 mice following a lethal challenge with S. typhimurium ATCC 14028, with interventions involving normal saline (NS), colostrum (COL), untreated Salmonella-challenged control, or calf-FMT transplanted and non-infected mice. Panel (D) demonstrates the Salmonella bacterial burden subsequent to the lethal challenge and feeding with NS or COL. Data are shown as mean ± standard deviation (SD). * p < 0.05; ** p < 0.001.