Parenteral nutrition inhibits tumor necrosis factor-alpha-mediated IgA response to injury

Parenteral nutrition (PN) increases the incidence of pneumonia in severely injured patients compared with enteral feeding (ENT). Injury induces an innate airway IgA response in severely injured patients; similar responses occur in mice. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) stimulate the production of polymeric immunoglobulin receptor (pIgR), the protein required to transport immunoglobulin A (IgA) to mucosal surfaces. We have shown that PN alters levels of lung and nasal passage IgA and several IgA-stimulating cytokines. We hypothesized that TNF-alpha and IL-1beta blockade, as well as PN, would blunt the airway IgA response to injury.

Male Institute of Cancer Research (ICR) mice were randomized to uninjured controls (n = 10) or to intra-peritoneal phosphate-buffered saline (PBS) (n = 9), antagonistic TNF-alpha antibody (100 mcg, n = 7), or antagonistic IL-1beta antibody (50 mcg, n = 8) 30 min prior to surgical stress with laparotomy and neck incisions. Mice were sacrificed at 8 h for nasal and bronchoalveolar lavage (NAL, BAL) to measure IgA by enzyme-linked immunosorbent assay. In a separate experiment, 12 mice underwent intravenous cannulation followed by chow (n = 5) or PN (n = 7) feeding for 5 days prior to the same stress and IgA measurement.

Injury significantly increased NAL and BAL IgA (225 +/- 104 ng) compared with baseline (145 +/- 38 ng; p = 0.01). Blockade of TNF-alpha eliminated the innate airway IgA response to injury (130 +/- 47 ng; p = 0.01), whereas IL-1beta blockade blunted and PN eliminated it completely.

Tumor necrosis factor-alpha is involved in the respiratory IgA immune response to injury. Both TNF-alpha blockade and PN impair this innate response, and blockade of IL-1beta impairs it to a degree. We hypothesize that these cytokines blunt this response via their known effects on the polymeric immunoglobulin receptor (pIgR), whereas the PN-induced deficit likely is multifactorial.