Parenteral Nutrition Inhibits Tumor Necrosis Factor-α-Mediated IgA Response to Injury

Background : 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- α ) and interleukin-1 beta (IL-1 β ) 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- α and IL-1 β blockade, as well as PN, would blunt the airway IgA response to injury. Methods : 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- α antibody (100 mcg, n = 7), or antagonistic IL-1 β 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. Results : Injury significantly increased NAL and BAL IgA (225 ± 104 ng) compared with baseline (145 ± 38 ng; p = 0.01). Blockade of TNF- α eliminated the innate airway IgA response to injury (130 ± 47 ng; p = 0.01), whereas IL-1 β blockade blunted and PN eliminated it completely. Conclusions : Tumor necrosis factor-alpha is involved in the respiratory IgA immune response to injury. Both TNF- α blockade and PN impair this innate response, and blockade of IL-1 β 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.