Innate Mucosal Immune System Response of BALB/c vs C57BL/6 Mice to Injury in the Setting of Enteral and Parenteral Feeding.
BACKGROUND
Outbred mice exhibit increased airway and intestinal immunoglobulin A (IgA) following injury when fed normal chow, consistent with humans. Parenteral nutrition (PN) eliminates IgA increases at both sites. Inbred mice are needed for detailed immunological studies; however, specific strains have not been evaluated for this purpose. BALB/c and C57BL/6 are common inbred mouse strains but demonstrate divergent immune responses to analogous stress. This study addressed which inbred mouse strain best replicates the outbred mouse and human immune response to injury.


METHODS
Intravenously cannulated mice received chow or PN for 5 days and then underwent sacrifice at 0 or 8 hours following controlled surgical injury (BALB/c: n = 16-21/group; C57BL/6: n = 12-15/group). Bronchoalveolar lavage (BAL) was analyzed by enzyme-linked immunosorbent assay for IgA, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, while small intestinal wash fluid (SIWF) was analyzed for IgA.


RESULTS
No significant increase in BAL IgA occurred following injury in chow- or PN-fed BALB/c mice (chow: P = .1; PN: P = .7) despite significant increases in BAL TNF-α and SIWF IgA (chow: 264 ± 28 vs 548 ± 37, P < .0001; PN: 150 ± 12 vs 301 ± 17, P < .0001). Injury significantly increased mucosal IgA in chow-fed C57BL/6 mice (BAL: 149 ± 33 vs 342 ± 87, P = .01; SIWF: 236 ± 28 vs 335 ± 32, P = .006) and BAL cytokines. After injury, PN-fed C57BL/6 mice exhibited no difference in BAL IgA (P = .9), BAL cytokines, or SIWF IgA (P = .1).


CONCLUSIONS
C57BL/6 mice exhibit similar airway responses to injury as outbred mice and humans, providing an appropriate model for studying mucosal responses to injury. The BALB/c mucosal immune system responds differently to injury and does not replicate the human injury response.
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Rebecca A
RA
Busch
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Mark A
MA
Jonker
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Department of Medicine-Gastroenterology, University of Chicago, Chicago, Illinois.
Joseph F
JF
Pierre
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Aaron F
AF
Heneghan
Veterans Administration Surgical Services, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin kudsk@surgery.wisc.edu.
Kenneth A
KA
Kudsk
D000818:Animals; D018893:Bronchoalveolar Lavage; D004750:Enteral Nutrition / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010288:Parenteral Nutrition / Q000379:methods*; D000072836:Surgical Wound / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007070:Immunoglobulin A; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
cytokines; immunonutrition; nutrition; parenteral nutrition; research and diseases; trauma