Systemic and cell-specific immune response to laparoscopic and open nephrectomy in porcine model.
OBJECTIVE
To determine differences in the systemic and cell-specific immune response to open and laparoscopic nephrectomy in the porcine model.


METHODS
Twenty male pigs (25-40 kg) were vaccinated with human adenovirus containing ovalbumin (Ova) and 3 weeks later underwent a sham procedure (N = 4), laparoscopic nephrectomy (LN)(N = 8), or open nephrectomy (ON) (N = 8). Blood was collected after anesthesia induction and immediately and 24 and 48 hours postoperatively and assayed for complete blood count (CBC), cortisol, and C-reactive protein (CRP). Natural killer (NK) cells were isolated and stimulated in vitro for 48 hours with polyinosinic:polycytidylic acid (Poly I:C) and interleukin (IL)-2 to determine cytotoxic activity. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry staining with CD8, CD4, and CD25 markers. Additional PBMCs were stimulated in vitro with Ova and ConA for 48 hours to measure the production of IL-10 and interferon (IFN)-gamma and a thymidine-incorporation assay to determine T-cell proliferation.


RESULTS
One animal in the ON group had signs of infection preoperatively and was removed from analysis. The LN took significantly longer than ON or sham nephrectomy (P = 0.002). Blood loss and animal weight were similar in the three groups. The CRP concentration increased more in the ON than the LN and sham-treatment groups in the first 48 hours (P = 0.01). No statistical differences were seen in the elevation of white blood cells or cortisol concentration. All groups demonstrated a decrease in the cytotoxic activity of NK cells postoperatively, with a significantly greater decrease in the sham-treated animals (P = 0.004). The LN group demonstrated greater T-cell activation than the ON and sham-treatment groups with both CD4(+) (P = 0.002) and CD8(+) (P = 0.028) cells increasing their expression of the activation marker CD25. The thymidine-incorporation assay demonstrated decreased T-cell proliferation in the ON group when stimulated with ConA (P = 0.014). Production of IL-10 decreased in the sham-treated and LN animals while increasing after ON. There was no difference in IFN-gamma among the groups.


CONCLUSIONS
In a porcine model, ON produces higher CRP concentrations postoperatively, a larger decrease in T-cell proliferation ability, and more IL-10 activity than LN or sham treatment. Animals undergoing LN demonstrated greater T-cell activation postoperatively. White blood cell counts, serum cortisol concentration, and production of IFN-gamma were similar among the groups. These findings suggest ON causes greater immune suppression than LN in the porcine model.
Duchene
David A
DA
Department of Urology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Gallagher
Brian L
BL
Ratliff
Timothy L
TL
Winfield
Howard N
HN
D000818:Animals; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D010535:Laparoscopy; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D009392:Nephrectomy; D034421:Sus scrofa
D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit