Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent

Abstract

SUMMARYMost studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin ( b -LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-b was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory outcome and this is also reflected by the systemic cytokine profile.

A novel model of sensitization and oral tolerance to peanut protein

“…Oral tolerance has been demonstrated after feeding of many different proteins, although the total number of antigens used experimentally is limited, and no model of oral tolerance to peanut proteins has been reported. In addition, most studies investigating oral tolerance use single, highly purified proteins and only few have studied the effects of feeding a mixture of proteins 7 . Requirements for tolerance induction may differ for single purified antigens and for the more physiologically relevant exposure to antigenic mixtures.…”

XP-828L in the Treatment of Mild to Moderate Psoriasis: Randomized, Double-Blind, Placebo-Controlled Study

“…8 Proteins contained in whey, such as b-lactoglobulin, a-lactalbumin, bovine serum albumin, lactoferrin, immunoglobulins, glycomacropeptide, and growth factors, are known to have health benefits 8 and to modulate the immune system. 11,12 In this study, the clinical benefit of XP-828L therapy in patients with mild to moderate psoriasis was shown mainly by the PGA score (primary efficacy variable), which was improved at day 56 in patients who received 5 g/d of the product. Also, the intragroup analysis revealed that both PGA and PASI scores were improved at day 56 in patients using XP-828L (see Tables 1 and 2), whereas no change was observed in the placebo group.…”

Oral gene application using chitosan-DNA nanoparticles induces transferable tolerance

“…To induce oral tolerance, mice were given an oral administration of 25 mg ovalbumin (OVA) in phosphate-buffered saline (PBS) on days 0 and 2 as the established treatment arm (1,25,41) or OVA-encoding chitosan-DNA NP (OVA-NP) containing 50 g plasmid-DNA (OVA/pcDNA3) on days 0, 2, 5, 7, and 9. Four groups of control animals received either a corresponding amount of chitosan-DNA NP encoding the enhanced green fluorescent protein (EGFP/pcDNA3.1) or pure chitosan solution, or 50 g naked OVA/ pcDNA3-plasmid, or PBS.…”

“…to reduce the levels of the cellular and humoral anti-OVA immune response (1,25,41). Application of OVA-NP suppressed the OVA-specific DTH response, IgG formation, and spleen cell proliferation as effectively as the treatment with OVA protein.…”