Route and Type of Nutrition Influence IgA-Mediating Intestinal Cytokines

Parenteral Nutrition Induces Organ Specific Alterations in Polymeric Immunoglobulin Receptor Levels

“…Conversely, intestinal pIgR levels drop with PN, while SI tissue homogenate IgA stays unchanged. The result of decreased pIgR expression in small intestine after PN feeding remains consistent with our hypothesis because small intestinal levels of IL-4 (a Th-2 cytokine that stimulates pIgR production) decreases in PN-fed mice [31]. This almost certainly implicates impaired transport as a main factor in the decrease of SI mucosal surface IgA levels with PN.…”

“…Lumen lavage specimens quantify the levels of IgA secreted onto mucosal surfaces by the epithelial cells while tissue homogenate IgA reflects IgA available for transport by pIgR, and pIgR protein levels measure an important component of the transport process. IgA levels in lavage specimens from the nasal passages and intestine dropped significantly with PN compared to chow fed mice replicating prior observations in regard to this particular outcome [25,31] and assuring that the model functioned and reliably reproduced conditions to interpret the new findings. Uniquely, this work demonstrates organ specific effects of enteral stimulation -or lack of enteral stimulation -on tissue (not luminal) IgA levels and the critical IgA transport protein, pIgR.…”

“…Such changes contribute to impaired mucosal immune function and integrity through several means including (among others) IgA production and IgA transport. We documented that PN decreases the number of T & B cells in the intestine [17] and lung (unpublished data), reduces the number antibody-forming cells in the upper respiratory tract (reduced production) in response to an acute infection [11], reduces levels of Th2-type IgA stimulating cytokines (reduced production), such as IL-4 and IL-10 [31], and reduces levels of pIgR protein within the intestinal mucosa (reduced transport) [26]. The overall effect of these alterations reduce available IgA production (reduced T & B cells and Th2-type cytokines) and transport (lowered intestinal pIgR levels) to impair or eliminate established anti-viral and antibacterial defenses in our murine model [13,16].…”

“…Secondly, we cannot sub-localize "tissue" IgA to the lamina propria (production) or to the epithelial cell layer (in transit) with current techniques. Without such an assay, the intestinal tissue homogenate IgA results should be interpreted with caution but we are reluctant to believe that IgA production would trend towards increase in PN animals given our previous data showing dramatic, 50% reductions in T & B cell numbers in the gut lamina propria [17] and decreases in IL-4 and IL-10, two important IgA stimulating cytokines, with PN [31]. Such data would suggest that IgA production is profoundly affected in the small intestine with PN.…”

“…PN feeding with lack of enteral stimulation results in reduced IgA levels at intestinal and respiratory mucosal surfaces as well changes in GALT cell phenotype. Specifically, PN reduces lamina propria and Peyer's patch T & B lymphocyte mass [17], intestinal Th-2 type IgA-stimulating cytokines [31] and intestinal pIgR levels [26]. Each alteration would appear to negatively impact luminal IgA levels by reducing production capacity (reduced cell mass & altered cytokines) or transport (reduced pIgR) of IgA from the site of production.…”