Skip to main content
Annals of Surgery logoLink to Annals of Surgery
. 1993 Dec;218(6):800–808. doi: 10.1097/00000658-199312000-00015

Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.

T Tadros 1, T Wobbes 1, T Hendriks 1
PMCID: PMC1243077  PMID: 8257231

Abstract

OBJECTIVE: This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.

Full text

PDF
800

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  2. Barbul A., Knud-Hansen J., Wasserkrug H. L., Efron G. Interleukin 2 enhances wound healing in rats. J Surg Res. 1986 Apr;40(4):315–319. doi: 10.1016/0022-4804(86)90193-9. [DOI] [PubMed] [Google Scholar]
  3. Breslin R. J., Barbul A., Kupper T. S., Knud-Hansen J. P., Wasserkrug H. L., Efron G. Generation of an anti-interleukin 2 factor in healing wounds. Arch Surg. 1988 Mar;123(3):305–308. doi: 10.1001/archsurg.1988.01400270039005. [DOI] [PubMed] [Google Scholar]
  4. Brunson M. E., Alexander J. W. Mechanisms of transfusion-induced immunosuppression. Transfusion. 1990 Sep;30(7):651–658. doi: 10.1046/j.1537-2995.1990.30790385527.x. [DOI] [PubMed] [Google Scholar]
  5. Damle N. K., Doyle L. V., Bender J. R., Bradley E. C. Interleukin 2-activated human lymphocytes exhibit enhanced adhesion to normal vascular endothelial cells and cause their lysis. J Immunol. 1987 Mar 15;138(6):1779–1785. [PubMed] [Google Scholar]
  6. DeCunzo L. P., Mackenzie J. W., Marafino B. J., Jr, Devereux D. F. The effect of interleukin-2 administration on wound healing in adriamycin-treated rats. J Surg Res. 1990 Nov;49(5):419–427. doi: 10.1016/0022-4804(90)90190-d. [DOI] [PubMed] [Google Scholar]
  7. Diegelmann R. F., Cohen I. K., Kaplan A. M. The role of macrophages in wound repair: a review. Plast Reconstr Surg. 1981 Jul;68(1):107–113. doi: 10.1097/00006534-198107000-00025. [DOI] [PubMed] [Google Scholar]
  8. Donohue J. H., Rosenberg S. A. The fate of interleukin-2 after in vivo administration. J Immunol. 1983 May;130(5):2203–2208. [PubMed] [Google Scholar]
  9. Edwards M. J., Schuschke D. A., Abney D. L., Miller F. N. Interleukin-2 acutely induces protein leakage from the microcirculation. J Surg Res. 1991 Jun;50(6):609–615. doi: 10.1016/0022-4804(91)90050-v. [DOI] [PubMed] [Google Scholar]
  10. Fahey T. J., 3rd, Sherry B., Tracey K. J., van Deventer S., Jones W. G., 2nd, Minei J. P., Morgello S., Shires G. T., Cerami A. Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1. Cytokine. 1990 Mar;2(2):92–99. doi: 10.1016/1043-4666(90)90002-b. [DOI] [PubMed] [Google Scholar]
  11. Fielding L. P., Stewart-Brown S., Blesovsky L., Kearney G. Anastomotic integrity after operations for large-bowel cancer: a multicentre study. Br Med J. 1980 Aug 9;281(6237):411–414. doi: 10.1136/bmj.281.6237.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ford H. R., Hoffman R. A., Wing E. J., Magee D. M., McIntyre L., Simmons R. L. Characterization of wound cytokines in the sponge matrix model. Arch Surg. 1989 Dec;124(12):1422–1428. doi: 10.1001/archsurg.1989.01410120068014. [DOI] [PubMed] [Google Scholar]
  13. George C. D., Morello P. J. Immunologic effects of blood transfusion upon renal transplantation, tumor operations, and bacterial infections. Am J Surg. 1986 Sep;152(3):329–337. doi: 10.1016/0002-9610(86)90269-2. [DOI] [PubMed] [Google Scholar]
  14. Granstein R. D., Deak M. R., Jacques S. L., Margolis R. J., Flotte T. J., Whitaker D., Long F. H., Amento E. P. The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model. J Invest Dermatol. 1989 Jul;93(1):18–27. doi: 10.1111/1523-1747.ep12277336. [DOI] [PubMed] [Google Scholar]
  15. Hendriks T., Mastboom W. J. Healing of experimental intestinal anastomoses. Parameters for repair. Dis Colon Rectum. 1990 Oct;33(10):891–901. doi: 10.1007/BF02051930. [DOI] [PubMed] [Google Scholar]
  16. Hesp F. L., Hendriks T., Lubbers E. J., deBoer H. H. Wound healing in the intestinal wall. A comparison between experimental ileal and colonic anastomoses. Dis Colon Rectum. 1984 Feb;27(2):99–104. doi: 10.1007/BF02553985. [DOI] [PubMed] [Google Scholar]
  17. Jensen L. S., Andersen A. J., Christiansen P. M., Hokland P., Juhl C. O., Madsen G., Mortensen J., Møller-Nielsen C., Hanberg-Sørensen F., Hokland M. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg. 1992 Jun;79(6):513–516. doi: 10.1002/bjs.1800790613. [DOI] [PubMed] [Google Scholar]
  18. Kaplan J., Sarnaik S., Gitlin J., Lusher J. Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions. Blood. 1984 Jul;64(1):308–310. [PubMed] [Google Scholar]
  19. Klempner M. S., Noring R., Mier J. W., Atkins M. B. An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med. 1990 Apr 5;322(14):959–965. doi: 10.1056/NEJM199004053221404. [DOI] [PubMed] [Google Scholar]
  20. Lotze M. T., Matory Y. L., Ettinghausen S. E., Rayner A. A., Sharrow S. O., Seipp C. A., Custer M. C., Rosenberg S. A. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol. 1985 Oct;135(4):2865–2875. [PubMed] [Google Scholar]
  21. Merluzzi V. J. Comparison of murine lymphokine-activated killer cells, natural killer cells, and cytotoxic T lymphocytes. Cell Immunol. 1985 Oct 1;95(1):95–104. doi: 10.1016/0008-8749(85)90298-9. [DOI] [PubMed] [Google Scholar]
  22. Nichols P. H., Ramsden C. W., Ward U., Sedman P. C., Primrose J. N. Perioperative immunotherapy with recombinant interleukin 2 in patients undergoing surgery for colorectal cancer. Cancer Res. 1992 Oct 15;52(20):5765–5769. [PubMed] [Google Scholar]
  23. Peterson J. M., Barbul A., Breslin R. J., Wasserkrug H. L., Efron G. Significance of T-lymphocytes in wound healing. Surgery. 1987 Aug;102(2):300–305. [PubMed] [Google Scholar]
  24. Rosenstein M., Yron I., Kaufmann Y., Rosenberg S. A. Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res. 1984 May;44(5):1946–1953. [PubMed] [Google Scholar]
  25. Salomon G. D., Kasid A., Cromack D. T., Director E., Talbot T. L., Sank A., Norton J. A. The local effects of cachectin/tumor necrosis factor on wound healing. Ann Surg. 1991 Aug;214(2):175–180. doi: 10.1097/00000658-199108000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schot J. D., Schuurman R. K. Blood transfusion suppresses cutaneous cell-mediated immunity. Clin Exp Immunol. 1986 Aug;65(2):336–344. [PMC free article] [PubMed] [Google Scholar]
  27. Schrock T. R., Deveney C. W., Dunphy J. E. Factor contributing to leakage of colonic anastomoses. Ann Surg. 1973 May;177(5):513–518. doi: 10.1097/00000658-197305000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shelby J., Hisatake G. Effect of ibuprofen and interleukin 2 on transfusion-induced suppression of cell-mediated immunity. Arch Surg. 1988 Nov;123(11):1397–1399. doi: 10.1001/archsurg.1988.01400350111017. [DOI] [PubMed] [Google Scholar]
  29. Stephan R. N., Kisala J. M., Dean R. E., Geha A. S., Chaudry I. H. Effect of blood transfusion on antigen presentation function and on interleukin 2 generation. Arch Surg. 1988 Feb;123(2):235–240. doi: 10.1001/archsurg.1988.01400260123016. [DOI] [PubMed] [Google Scholar]
  30. Tadros T., Wobbes T., Hendriks T. Blood transfusion impairs the healing of experimental intestinal anastomoses. Ann Surg. 1992 Mar;215(3):276–281. doi: 10.1097/00000658-199203000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tartter P. I., Quintero S., Barron D. M. Perioperative blood transfusion associated with infectious complications after colorectal cancer operations. Am J Surg. 1986 Nov;152(5):479–482. doi: 10.1016/0002-9610(86)90207-2. [DOI] [PubMed] [Google Scholar]
  32. Waymack J. P., Balakrishnan K., McNeal N., Gonce S., Miskell P., Warden G. D., Alexander J. W. Effect of blood transfusions on macrophage-lymphocyte interaction in an animal model. Ann Surg. 1986 Dec;204(6):681–685. doi: 10.1097/00000658-198612000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Waymack J. P., Gallon L., Barcelli U., Trocki O., Alexander J. W. Effect of blood transfusions on immune function. III. Alterations in macrophage arachidonic acid metabolism. Arch Surg. 1987 Jan;122(1):56–60. doi: 10.1001/archsurg.1987.01400130062009. [DOI] [PubMed] [Google Scholar]
  34. Waymack J. P., Warden G. D., Alexander J. W., Miskell P., Gonce S. Effect of blood transfusion and anesthesia on resistance to bacterial peritonitis. J Surg Res. 1987 May;42(5):528–535. doi: 10.1016/0022-4804(87)90028-x. [DOI] [PubMed] [Google Scholar]
  35. Wobbes T., Bemelmans B. L., Kuypers J. H., Beerthuizen G. I., Theeuwes A. G. Risk of postoperative septic complications after abdominal surgical treatment in relation to perioperative blood transfusion. Surg Gynecol Obstet. 1990 Jul;171(1):59–62. [PubMed] [Google Scholar]
  36. Wood M. L., Gottschalk R., Monaco A. P. Effect of blood transfusion on IL-2 production. Transplantation. 1988 May;45(5):930–935. doi: 10.1097/00007890-198805000-00018. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES