Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1995 Oct;222(4):534–548. doi: 10.1097/00000658-199522240-00011

The delayed hypersensitivity response and host resistance in surgical patients. 20 years later.

N V Christou 1, J L Meakins 1, J Gordon 1, J Yee 1, M Hassan-Zahraee 1, C W Nohr 1, H M Shizgal 1, L D MacLean 1
PMCID: PMC1234888  PMID: 7574933

Abstract

OBJECTIVE: A 20-year follow-up was conducted on research into the implications of a lack of a delayed-type hypersensitivity (DTH) skin test response among surgical patients. SUMMARY BACKGROUND DATA: The authors' original report showed that a failed DTH response was associated with increased hospital mortality, but the role of specific and nonspecific host defense elements, comorbid factors, nutritional supplementation, and the mechanism for anergy in this adverse outcome was unknown. METHODS: A data base of 4292 patients was analyzed and reported on individual studies designed to answer some of the above questions. RESULTS: Prospective studies showed a strong association between the DTH response and mortality: reactive patients, 2.9% (75/2576); anergic patients, 20.9% (239/1142, chi square = 265, p < 0.0000001). Antibody response to protein antigens was reduced in anergic patients. Antibody response to polysaccharide antigens was normal in all patients. The hallmark of anergy is a lack of T cells in the skin, as measured by mRNA signal (CD3) for T cells. The nonspecific component of host defense, as measured by circulating and exudate polymorphonuclear cell function, showed no statistically significant difference between elective reactive and elective anergic patients. Notwithstanding some mild malnutrition in anergic patients, parental nutrition failed to correct the DTH response or many of the cellular immune functions measured. CONCLUSIONS: Over the last 5 years, because of a reduction in overall patient mortality, the contribution of a reduced DTH response to septic related mortality has lost statistical significance in elective surgical patients. A reduced DTH response maintains its strong association to sepsis-related mortality in intensive care/trauma patients, and this is the group on which future research efforts should be concentrated.

Full text

PDF
534

Images in this article

537Figure 1.
on p.537
544Figure 3.
on p.544

Selected References

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

  1. Baker P. J., Amsbaugh D. F., Stashak P. W., Caldes G., Prescott B. Regulation of the antibody response to pneumococcal polysaccharide by thymus-derived cells. Rev Infect Dis. 1981 Mar-Apr;3(2):332–341. doi: 10.1093/clinids/3.2.332. [DOI] [PubMed] [Google Scholar]
  2. Barker J. N., Allen M. H., MacDonald D. M. The effect of in vivo interferon-gamma on the distribution of LFA-1 and ICAM-1 in normal human skin. J Invest Dermatol. 1989 Oct;93(4):439–442. doi: 10.1111/1523-1747.ep12284016. [DOI] [PubMed] [Google Scholar]
  3. Bos J. D., Zonneveld I., Das P. K., Krieg S. R., van der Loos C. M., Kapsenberg M. L. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin. J Invest Dermatol. 1987 May;88(5):569–573. doi: 10.1111/1523-1747.ep12470172. [DOI] [PubMed] [Google Scholar]
  4. Brown R., Bancewicz J., Hamid J., Patel N. J., Ward C. A., Farrand R. J., Pumphrey R. S., Irving M. Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality. Br Med J (Clin Res Ed) 1982 Mar 20;284(6319):851–853. doi: 10.1136/bmj.284.6319.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buzby G. P. Overview of randomized clinical trials of total parenteral nutrition for malnourished surgical patients. World J Surg. 1993 Mar-Apr;17(2):173–177. doi: 10.1007/BF01658923. [DOI] [PubMed] [Google Scholar]
  6. Casey J., Flinn W. R., Yao J. S., Fahey V., Pawlowski J., Bergan J. J. Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations. Surgery. 1983 Jun;93(6):822–827. [PubMed] [Google Scholar]
  7. Christou N. V., Meakins J. L. Neutrophil function in anergic surgical patients: neutrophil adherence and chemotaxis. Ann Surg. 1979 Nov;190(5):557–564. doi: 10.1097/00000658-197911000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Christou N. V., Tellado J. M. In vitro polymorphonuclear neutrophil function in surgical patients does not correlate with anergy but with "activating" processes such as sepsis or trauma. Surgery. 1989 Oct;106(4):718–724. [PubMed] [Google Scholar]
  9. Dallman M. J., Montgomery R. A., Larsen C. P., Wanders A., Wells A. F. Cytokine gene expression: analysis using northern blotting, polymerase chain reaction and in situ hybridization. Immunol Rev. 1991 Feb;119:163–179. doi: 10.1111/j.1600-065x.1991.tb00583.x. [DOI] [PubMed] [Google Scholar]
  10. Davies A. J., Carter R. L., Leuchars E., Wallis V., Dietrich F. M. The morphology of immune reactions in normal, thymectomized and reconstituted mice. 3. Response to bacterial antigens: salmonellar flagellar antigen and pneumococcal plysaccharide. Immunology. 1970 Dec;19(6):945–957. [PMC free article] [PubMed] [Google Scholar]
  11. Foster C. A., Yokozeki H., Rappersberger K., Koning F., Volc-Platzer B., Rieger A., Coligan J. E., Wolff K., Stingl G. Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor. J Exp Med. 1990 Apr 1;171(4):997–1013. doi: 10.1084/jem.171.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harvey K. B., Moldawer L. L., Bistrian B. R., Blackburn G. L. Biological measures for the formulation of a hospital prognostic index. Am J Clin Nutr. 1981 Oct;34(10):2013–2022. doi: 10.1093/ajcn/34.10.2013. [DOI] [PubMed] [Google Scholar]
  13. Johnson W. C., Ulrich F., Mequid M. M., Lepak N., Bowe P., Harris P., Alberts L. H., Nabseth D. C. Role of delayed hypersensitivity in predicting postoperative morbidity and mortality. Am J Surg. 1979 Apr;137(4):536–542. doi: 10.1016/0002-9610(79)90127-2. [DOI] [PubMed] [Google Scholar]
  14. Kienlen J., Chardon P., Nury G., Lubrano J. F., Messmer J. C., du Cailar J. Etude de l'hypersensibilité cutanée retardée par le multitest chez une population de réanimation polyvalente. Ann Anesthesiol Fr. 1981;22(3):285–291. [PubMed] [Google Scholar]
  15. Leung J. C., Lai C. K., Chui Y. L., Ho R. T., Chan C. H., Lai K. N. Characterization of cytokine gene expression in CD4+ and CD8+ T cells after activation with phorbol myristate acetate and phytohaemagglutinin. Clin Exp Immunol. 1992 Oct;90(1):147–153. doi: 10.1111/j.1365-2249.1992.tb05847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MacLean L. D., Meakins J. L., Taguchi K., Duignan J. P., Dhillon K. S., Gordon J. Host resistance in sepsis and trauma. Ann Surg. 1975 Sep;182(3):207–217. doi: 10.1097/00000658-197509000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. MacPhee M. J., Rode H., Broadhead M., Christou N. V., Meakins J. L., Gordon J. Skin window chambers, a novel method for recovering the cells involved in delayed-type hypersensitivity. J Immunol Methods. 1987 Nov 5;103(2):267–273. doi: 10.1016/0022-1759(87)90299-7. [DOI] [PubMed] [Google Scholar]
  18. MacPhee M., Christou N. V., Gordon J., Chartrand L., Rode H. Quantitative and qualitative study of the restoration by cytokines of mononuclear cell delivery to skin test sites in anergic surgical patients. Arch Surg. 1988 Dec;123(12):1470–1473. doi: 10.1001/archsurg.1988.01400360040005. [DOI] [PubMed] [Google Scholar]
  19. Mackay C. R. Lymphocyte homing. Skin-seeking memory T cells. Nature. 1991 Feb 28;349(6312):737–738. doi: 10.1038/349737a0. [DOI] [PubMed] [Google Scholar]
  20. Moore F. A., Moore E. E., Kudsk K. A., Brown R. O., Bower R. H., Koruda M. J., Baker C. C., Barbul A. Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding. J Trauma. 1994 Oct;37(4):607–615. doi: 10.1097/00005373-199410000-00014. [DOI] [PubMed] [Google Scholar]
  21. Morath M. A., Miller S. F., Finley R. K., Jr Nutritional indicators of postburn bacteremic sepsis. JPEN J Parenter Enteral Nutr. 1981 Nov-Dec;5(6):488–491. doi: 10.1177/0148607181005006488. [DOI] [PubMed] [Google Scholar]
  22. Mullen J. L., Gertner M. H., Buzby G. P., Goodhart G. L., Rosato E. F. Implications of malnutrition in the surgical patient. Arch Surg. 1979 Feb;114(2):121–125. doi: 10.1001/archsurg.1979.01370260011001. [DOI] [PubMed] [Google Scholar]
  23. Nickoloff B. J. Role of interferon-gamma in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Arch Dermatol. 1988 Dec;124(12):1835–1843. [PubMed] [Google Scholar]
  24. Nohr C. W., Christou N. V., Rode H., Gordon J., Meakins J. L. In vivo and in vitro humoral immunity in surgical patients. Ann Surg. 1984 Sep;200(3):373–380. doi: 10.1097/00000658-198409000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rode H. N., Christou N. V., Bubenik O., Superina R., Gordon J., Meakins J. L., MacLean L. D. Lymphocyte function in anergic patients. Clin Exp Immunol. 1982 Jan;47(1):155–161. [PMC free article] [PubMed] [Google Scholar]
  26. Rode H. N., Christou N. V., Bubenik O., Superina R., Gordon J., Meakins J. L., MacLean L. D. Lymphocyte function in anergic patients. Clin Exp Immunol. 1982 Jan;47(1):155–161. [PMC free article] [PubMed] [Google Scholar]
  27. Rode H. N., Puyana J. C., Macphee M., Meakins J. L., Christou N., Gordon J. Role of cytokines in the restoration of the delayed-type hypersensitivity reaction of anergic patients. Clin Exp Immunol. 1988 Jan;71(1):159–163. [PMC free article] [PubMed] [Google Scholar]
  28. Yee J., Giannias B., Kapadia B., Chartrand L., Christou N. V. Exudative neutrophils. Modulation of microbicidal function in the inflammatory microenvironment. Arch Surg. 1994 Jan;129(1):99–105. doi: 10.1001/archsurg.1994.01420250111014. [DOI] [PubMed] [Google Scholar]
  29. Zimmerli W., Seligmann B., Gallin J. I. Exudation primes human and guinea pig neutrophils for subsequent responsiveness to the chemotactic peptide N-formylmethionylleucylphenylalanine and increases complement component C3bi receptor expression. J Clin Invest. 1986 Mar;77(3):925–933. doi: 10.1172/JCI112391. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES