KMP01D Demonstrates Beneficial Anti-inflammatory Effects on Immune Cells: An ex vivo Preclinical Study of Patients With Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) is frequently associated with dysbiosis of the gut microbiome which, together with a compromised gut barrier, can result in perioperative endotoxin leakage into the circulation. Constant local and systemic inflammatory activity is suggested to facilitate metastases formation. Previous studies have pointed to the capacity of a colostrum preparation to neutralize endotoxins within the gastrointestinal tract which could ameliorate associated inflammatory responses and tumor recurrence in affected patients. This study aimed to examine the effects of the colostrum preparation, KMP01D, on the inflammatory activity of patient-derived immune cells.Methods: The effects of KMP01D on pro-/anti-inflammatory cytokine responses and apoptosis were examined ex vivo using immune cells from CRC patients (stages I-IV, n = 48). The expression of CD14, CD68, Toll-like receptor (TLR)4, and insulin-like growth factor (IGF)-1 was also analyzed.Results: KMP01D increased interleukin (IL)-10 and IL-13 anti-inflammatory cytokine expression in patient-derived peripheral blood mononuclear cells (PBMCs). Interestingly, KMP01D also decreased the secretion of IL-1β, IL-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-12 inflammatory cytokines, and IGF-1 in these cells. Moreover, CD14 and TLR4 expression involved in endotoxin signaling was downregulated in PBMCs and tumor-derived cells. Apoptosis of immune cells and tumor-derived cells was likewise enhanced with KMP01D. Addition of vitamin D3 as a cofactor demonstrated enhanced anti-inflammatory effects.Conclusions: KMP01D demonstrated beneficial ex vivo effects on inflammatory cytokine responses in PBMCs and enhanced apoptosis of immune cells from CRC patients. In line with previous clinical trials, we present new evidence endorsing KMP01D as a treatment strategy to regulate stage-dependent local and systemic inflammation in CRC patients.

Value Research of NLR, PLR, and RDW in Prognostic Assessment of Patients with Colorectal Cancer

“…Add up 0, 20, 40, 60, and 80 months to correspond to NLR, PLR, and RDW survival rate, respectively. PLR normal range [ 5 ] is (1.5 ± 0.9), PLR > 103.7 represents the PLR abnormality; NLR normal range is (1.5 ± 0.9), NLR > 2.4 represents the NLR abnormalities; RDW normal range is (10.0 ± 2.6) FL, NLR > 12.58FL represents the RDW anomaly.…”

Bioactive compounds, nutritional profile and health benefits of colostrum: a review

“…The immunoglobulins derived from colostrum are capable to fetch the pathogens with microphages, modify the microflora of intestine, stimulate the activation of B and T cell, and prevent the binding of pathogen to the host cell along with the localized production of IgA (Ulfman et al 2018 ). Gasser et al ( 2018 ) studied that the combination of polyvalent from of immunoglobulins with Vitamin D3 can beneficially impact on the systemic inflammation occurring in the patients suffering from the colorectal cancer by promoting the level of cytokines which have anti-inflammatory activity. The IgG is effective against the infections of gastrointestinal and respiratory tract like allergic asthma by their improved epithelial integrity as a barrier (Anderson et al 2019 ).…”

Diverse Immune Effects of Bovine Colostrum and Benefits in Human Health and Disease

“…The tumor microenvironment supports the migration process of tumor cells and their seeding in distant organs such as the liver and the lungs. Orally administered colostrum polyvalent immunoglobulins (KMP01D) increased interleukin (IL)-10 and IL-13 anti-inflammatory cytokine expression in patient-derived peripheral blood mononuclear cells (PBMCs) [23]. Interestingly, KMP01D also decreased the secretion of IL-1β, IL-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-12 inflammatory cytokines, and IGF-1 in these cells [23].…”

“…Orally administered colostrum polyvalent immunoglobulins (KMP01D) increased interleukin (IL)-10 and IL-13 anti-inflammatory cytokine expression in patient-derived peripheral blood mononuclear cells (PBMCs) [23]. Interestingly, KMP01D also decreased the secretion of IL-1β, IL-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-12 inflammatory cytokines, and IGF-1 in these cells [23]. Moreover, CD14 and TLR4 expression involved in endotoxin signaling was downregulated in PBMCs and tumor-derived cells.…”