Is There a Role for the Enteral Administration of Serum-Derived Immunoglobulins in Human Gastrointestinal Disease and Pediatric Critical Care Nutrition?

Abstract

Twenty years ago, there was profound, international interest in developing oral human, bovine, or chicken egg-derived immunoglobulin (Ig) for the prevention and nutritional treatment of childhood malnutrition and gastrointestinal disease, including acute diarrhea and necrotizing enterocolitis. Although such Ig products were shown to be effective, with both nutritional and antidiarrheal benefits, interest waned because of their cost and because of the perceived risk of bovine serum encephalitis (BSE). BSE is no longer considered a barrier to use of oral Ig, because the WHO has declared the United States to be BSE-free since the early 2000s. Low-cost bovine-derived products with high Ig content have been developed and are regulated as medical foods. These new products, called serum bovine Igs (SBIs), facilitate the management of chronic or severe gastrointestinal disturbances in both children and adults and are regulated by the US Food and Drug Administration. Well-established applications for use of SBIs include human immunodeficiency virus (HIV)-associated enteropathy and diarrhea-predominant irritable bowel syndrome. However, SBIs and other similar products could potentially become important components of the treatment regimen for other conditions, such as inflammatory bowel disease, by aiding in disease control without immunosuppressive side effects. In addition, SBIs may be helpful in conditions associated with the depletion of circulating and luminal Igs and could potentially play an important role in critical care nutrition. The rationale for their use is to facilitate intraluminal microbial antibody coating, an essential process in immune recognition in the gut which is disturbed in these conditions, thereby leading to intestinal inflammation. Thus, oral Ig may emerge as an important "add-on" therapy for a variety of gastrointestinal and nutritional problems during the next decade.

Keywords: Ig; colitis; diarrhea; enteropathy; gut barrier function; inflammatory bowel disease; irritable bowel syndrome; malnutrition; serum bovine Ig.

FIGURE 1

Proposed mechanisms of action of oral Ig SBI. (1) SBI binds luminal bacteria and their endotoxins (LPS), providing a level of immune exclusion. (2) Reduced transepithelial antigen absorption across the small and/or large intestine has been linked to reduced immune activation, including effects on B cells, T cells, and macrophages. (3) SBI may interact with healthy commensals to induce tolerogenic DCs. Shown is a tolerogenic DC signaling to CD4⁺ helper T cells, which are known to communicate with Treg/Tr1 cells to produce anti-inflammatory cytokine IL-10. Immune homeostasis may reduce production of pro-inflammatory cytokines such as TNF-α and would increase production of IL-10. CD4⁺, cluster of differentiation 4; DC, dendritic cell; LP, lamina propria; SBI, serum-derived bovine Ig; Treg, Foxp3⁺ regulatory T cell; Tr1, Foxp3⁻ IL10-producing regulatory T cell.