Réjean Drouin

A Bovine Whey Protein Extract Stimulates Human Neutrophils to Generate Bioactive IL-1Ra through a NF-κB- and MAPK-Dependent Mechanism

Innate immunity depends on the efficiency of neutrophils to be activated rapidly to restore homeostasis. It can benefit from priming agents that enhance neutrophil capacity to respond more efficiently to a subsequent stimulation. Among natural products, a bovine whey protein extract (WPE) has been shown to prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis, oxidative burst, and degranulation. These leukocytes are also an important source of cytokines, some of which have antiinflammatory functions. We investigated the role of WPE, as well as its mechanisms of action, on the production of interleukin (IL)-1 receptor antagonist (IL-1Ra) by neutrophils in vitro. WPE dose-dependently stimulated de novo synthesis and release of IL-1Ra by normal human blood neutrophils. Among the major proteins present in WPE, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the only active components. They had additive effects that exactly reproduced those of WPE. Similarly to WPE, they also stimulated the accumulation of IL-1beta, IL-8, IL-6, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha. However, neutrophils incubated with WPE, beta-LG, and alpha-LA produced IL-1Ra in excess of IL-1beta and the ratio IL-1Ra:IL-1beta increased linearly. The amounts of IL-1Ra stimulated by WPE or beta-LG + alpha-LA significantly reduced the IL-1 activity in EL4 cells. Inhibitors of p38 and extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and nuclear factor-kappaB cascades reduced neutrophil production of IL-1Ra. Our data suggest that WPE, through beta-LG + alpha-LA, has immunomodulatory properties and the potential to increase host defenses.

XP-828L (Dermylex), a new whey protein extract with potential benefit for mild to moderate psoriasis

Natural health products (NHPs) or complementary and alternative medicine (CAM) are commonly used to prevent disorders or support the usual treatments of many diseases. XP-828L, a whey protein extract, has demonstrated potential benefits for the treatment of mild to moderate psoriasis. The aim of this study was to analyze further clinical data that demonstrated the clinical benefits and safety of the XP-828L in patients with psoriasis and the potential mechanism of action of this product in vitro. Oral administration (2.5 g, twice a day, over 112 days) of XP-828L in 42 human subjects with mild to moderate psoriasis improved their PGA scores (physicians global assessment). Moreover, no significant changes in haematology or hepatic and renal parameters were observed throughout the study period, indicating the safety of the product. In vitro experiments showed that XP-828L decreased the proliferation of concanavalin A (ConA)-stimulated murine splenocytes and their production of interleukin (IL)-2 and interferon (IFN)-gamma. Although the in vivo mechanism of action of XP-828L remains unknown, XP-828L represents an NHP to be used as an alternative or concomitant treatment for mild to moderate psoriasis and potentially for other immune-mediated diseases.