title: Parenteral nutrition inhibits tumor necrosis factor-alpha-mediated IgA response to injury.
abstract: 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-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.
  
  
  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-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, University of Wisconsin-Madison College of Medicine and Public Health, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53792-7375, USA.
authors: Joshua L
authors: JL
authors: Hermsen
authors: Yoshifumi
authors: Y
authors: Sano
authors: F Enrique
authors: FE
authors: Gomez
authors: Yoshinori
authors: Y
authors: Maeshima
authors: Woodae
authors: W
authors: Kang
authors: Kenneth A
authors: KA
authors: Kudsk
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007070:Immunoglobulin A / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017817:Nasal Lavage Fluid / Q000276:immunology; D010288:Parenteral Nutrition; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha