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Prevention of Posttraumatic Alterations in Lymphocyte Subpopulations in Mice by Immunomodulating Drugs

Prevention of Posttraumatic Alterations in Lymphocyte Subpopulations in Mice by Immunomodulating... Abstract • Infection is a major cause of morbidity and mortality in traumatized victims, as well as an unfortunate complication following surgical procedures. The incidence of such infections is probably related to immune suppression occurring after severe trauma and surgery. Cell-mediated immunity is an arm of immunity that is probably important in defense against bacterial as well as fungal and viral infections. The status of cell-mediated immunity appears to be reflected by the helper/inducer to suppressor/cytotoxic lymphocyte (Ly1+/Ly2+ in the mouse model) ratio. A depressed ratio has been shown to correlate with other measures of suppressed immunity. Using monoclonal antibodies and immunofluorescent analysis, splenic lymphocyte subpopulations were enumerated at different intervals after injury in mice receiving various injuries (laparotomy, 40% liver resection, burn injury covering 20% of total body surface area, and crush injury—amputation of hind limb). An immediate fall in the Ly1+/Ly2+ ratio was observed following the most severe injuries, namely, liver resection, burn, and crush injury—amputation, but not following laparotomy. Changes in the ratio were reflected by both decreases in helper populations (Ly1+ ) and increases in suppressor populations (Ly2+). Prostaglandins and histamines have been implicated as possible mediators in producing down-regulation of the immune system. Posttraumatic lymphocyte alterations were prevented in crush injury—amputation group mice when drugs (ibuprofen and cimetidine) to block such mediators were administered prior to trauma; changes were also prevented by administering cyclophosphamide, a drug which in low dose might inhibit proliferation of suppressor lymphocyte populations. (Arch Surg 1986;121:116-122) References 1. MacLean LD: Host resistance in surgical patients . J Trauma 1979;19: 297-304.Crossref 2. Miller SE, Miller CL, Trunkey DD: The immune consequences of trauma . Surg Clin North Am 1982;62:167-182. 3. Nohr CW, Christou NV, Rode H, et al: In vivo and in vitro humoral immunity in surgical patients . Ann Surg 1984;200:373-380.Crossref 4. Superina R, Meakins JL: Delayed hypersensitivity, anergy, and the surgical patient . J Surg Res 1984;37:151-174.Crossref 5. Wang BS, Heacock EH, Wu AVO, et al: Generation of suppressor cells in mice after surgical trauma . J Clin Invest 1980;66:200-209.Crossref 6. Lundy J, Ford CM: Surgery, trauma, and immune suppression: Evolving the mechanism . Ann Surg 1983;197:434-438.Crossref 7. Meakins JL, Pietsch JB, Bubenick O, et al: Delayed hypersensitivity: Indicator of acquired failure of host defenses in sepsis and trauma . Ann Surg 1977;186:241-250.Crossref 8. Pietsch JB, Meakins JL, Cotto D, et al: Delayed hypersensitivity responses: The effect of surgery . J Surg Res 1977;22:228-230.Crossref 9. Meakins JL, McLean AP, Kelly R, et al: Delayed hypersensitivity and neutrophil chemotaxis: Effect of trauma . J Trauma 1978;18:240-247.Crossref 10. Buffone V, Meakins JL, Christou NV: Neutrophil function in surgical patients: Relationship to adequate bacterial defenses . Arch Surg 1984;119: 39-43.Crossref 11. Allgower M, Durig M, Wolff G: Infection and trauma . Surg Clin North Am 1980;60:133-144. 12. Reinherz EL, Schlossman SF: Regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings . N Engl J Med 1980;303:370-373.Crossref 13. Kung PC, Goldstein G, Reinherz EL, et al: Monoclonal antibodies defining distinctive human T-cell surface antigens . Science 1979;206:347-349.Crossref 14. Lehmann PF, Gibbons J, Senitzer D, et al: T-lymphocyte abnormalities in disseminated histoplasmosis . Am J Med 1983;75:790-794.Crossref 15. Williams RC, Koster FT, Kilpatrick KA: Alterations in lymphocyte cell surface markers during various human infections . Am J Med 1983;75: 807-816.Crossref 16. Antonacci AC, Good RA, Gupta S: T-cell subpopulations following thermal injury . Surg Gynecol Obstet 1982;155:1-8. 17. Zapata-Sirvent RL, Hansbrough JF: Postburn immunosuppression in an animal model: III. Maintenance of normal helper and suppressor lymphocyte subpopulations by immunomodulating drugs . Surgery 1985;97: 721-727. 18. Hansbrough JF, Peterson V, Kortz E, et al: Postburn immunosuppression in an animal model: Monocyte dysfunction induced by burned tissue . Surgery 1983;93:415-423. 19. Howard RJ, Simmons RL: Acquired immunologic defects after trauma and surgical procedures . Surg Gynecol Obstet 1974;139:771-782. 20. Nohr CW, Christou NV, Rode H, et al: In vivo and in vitro humoral immunity in surgical patients . Ann Surg 1984;200:373-380.Crossref 21. Buffone V, Meakins JL,Christou NV: Neutrophil function in surgical patients: Relationship to adequate bacterial defenses . Arch Surg 1984;119: 39-43.Crossref 22. Deitch EA, Gelder F, McDonald JC: Sequential prospective analysis of the nonspecific host defense system after thermal injury . Arch Surg 1984;119:83-89.Crossref 23. Saba TM, Diluzio NR: Surgical stress and reticuloendothelial function . Surgery 1968;65:802-807. 24. Hansbrough JF, Bender EM, Zapata-Sirvent R, et al: Altered helper and suppressor lymphocyte populations in surgical patients: A measure of post-operative immunosuppression . Am J Surg 1984;148:303-307.Crossref 25. Johnson WC, Ulrich F, Muguid MM, et al: Role of delayed hypersensitivity in predicting postoperative morbidity and mortality . Am J Surg 1979;137:536-542.Crossref 26. Keane RM, Birmingham W, Shatney CM, et al: Prediction of sepsis in the multitraumatic patient by assays of lymphocyte responsiveness . Surg Gynecol Obstet 1983;156:163-167. 27. McLaughlin GA, Wu AV, Saporoschetz I, et al: Correlation between anergy and a circulating immunosuppressive factor following major surgical trauma . Ann Surg 1979;190:297-304.Crossref 28. Hansbrough JF, Peterson V, Zapata-Sirvent R, et al: Postburn immunosuppression in an animal model: II. Restoration of immunity by immunomodulating drugs . Surgery 1984;95:290-295. 29. Bohnen JM, Christou NV, Chiasson L, et al: Anergy secondary to sepsis in rats: Relation to outcome . Arch Surg 1984;119:117-120.Crossref 30. Rocklin RE, Bendtzen K, Greineder D: Mediators of immunity: Lymphokines and monokines . Adv Immunol 1980;29:55-127. 31. Payne J, Hayden P, Meyer HJ, et al: Observed differences in postoperative lymphocyte transformation are explained by patient and population variations . Am J Surg 1984;147:237-242.Crossref 32. Boudet RA, Morse PA, Watts LM: An analysis of human peripheral lymphocytes to phytohemagglutinin lymphoblastogenesis in whole blood . Surg Gynecol Obstet 1978;146:609-616. 33. Graybill JR, Alford RH: Variability of sequential studies of lymphocyte blastogenesis in normal adults . Clin Exp Immunol 1976;25:28-35. 34. Gershon RK, Leibhaver SA, Ryn S: T-cell regulation of T-cell responses to antigen . Immunology 1974;26:909-923. 35. Reinherz EL, Schlossman SF: Regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings . N Engl J Med 1980;303:370-373.Crossref 36. Munster AM: Post-traumatic immunosuppression is due to activation of suppressor cells . Lancet 1976;1:1329.Crossref 37. Wood JJ, Rodrick ML, O'Mahony JB, et al: Inadequate interleukin production: A fundamental immunological deficiency in patients with major burns . Ann Surg 1984;200:311-320.Crossref 38. Beer DJ, Matloff SM, Rocklin RE: The influence of histamine on immune and inflammatory responses . Adv Immunol 1984;35:209-268. 39. Griswold DE, Alessi S, Badger AM, et al: Inhibition of suppressor cell expression by histamine type (H2) receptor antagonists . J Immunol 1984;132:3054-3057. 40. Goodwin JS: Immunologic effects of nonsteroidal anti-inflammatory drugs . Am J Med 1981;70:7-15.Crossref 41. Webb DR, Osheroff PL: Antigen stimulation of prostaglandin synthesis and control of immune responses . Proc Natl Acad Sci USA 1976;73: 1300-1309.Crossref 42. Askenase PW, Hayden BJ, Gershon RK: Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses . J Exp Med 1975;141:697-702.Crossref 43. Gill HK, Liew FY: Regulation of DTH-effect of cyclophosphamide on suppressor cells for DTH to sheep red blood cells in mice . Eur J Immunol 1978;8:172-176.Crossref 44. Schwartz A, Askenase PW, Gershon RK: Regulation of DTH reactions by cyclophosphamide-sensitive T cells . J Immunol 1978;121:1573-1577. 45. Kupper TS, Green DR, Chaudry IH, et al: A cyclophosphamide-sensitive T cell circuit induced by thermal injury . Surgery 1984;95:699-705. 46. Bender EM, Hansbrough JF, Zapata-Sirvent R, et al: Restoration of immunity in burned mice by cimetidine . J Trauma 1985;25:131-137.Crossref 47. Gershon RK, Eardley DD, Durum S, et al: Contrasuppression: A novel immunoregulatory activity . J Exp Med 1981;153:1533-1546.Crossref 48. Swain SL, Dutton RW: Mouse T-lymphocyte sub-populations: Relationships between function and Lyt antigen phenotype , in Inglis JR (ed): T Lymphocytes Today . New York, Elsevier Science Publishing Co Inc, 1983. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Prevention of Posttraumatic Alterations in Lymphocyte Subpopulations in Mice by Immunomodulating Drugs

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Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1986.01400010130018
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Abstract

Abstract • Infection is a major cause of morbidity and mortality in traumatized victims, as well as an unfortunate complication following surgical procedures. The incidence of such infections is probably related to immune suppression occurring after severe trauma and surgery. Cell-mediated immunity is an arm of immunity that is probably important in defense against bacterial as well as fungal and viral infections. The status of cell-mediated immunity appears to be reflected by the helper/inducer to suppressor/cytotoxic lymphocyte (Ly1+/Ly2+ in the mouse model) ratio. A depressed ratio has been shown to correlate with other measures of suppressed immunity. Using monoclonal antibodies and immunofluorescent analysis, splenic lymphocyte subpopulations were enumerated at different intervals after injury in mice receiving various injuries (laparotomy, 40% liver resection, burn injury covering 20% of total body surface area, and crush injury—amputation of hind limb). An immediate fall in the Ly1+/Ly2+ ratio was observed following the most severe injuries, namely, liver resection, burn, and crush injury—amputation, but not following laparotomy. Changes in the ratio were reflected by both decreases in helper populations (Ly1+ ) and increases in suppressor populations (Ly2+). Prostaglandins and histamines have been implicated as possible mediators in producing down-regulation of the immune system. Posttraumatic lymphocyte alterations were prevented in crush injury—amputation group mice when drugs (ibuprofen and cimetidine) to block such mediators were administered prior to trauma; changes were also prevented by administering cyclophosphamide, a drug which in low dose might inhibit proliferation of suppressor lymphocyte populations. (Arch Surg 1986;121:116-122) References 1. MacLean LD: Host resistance in surgical patients . J Trauma 1979;19: 297-304.Crossref 2. Miller SE, Miller CL, Trunkey DD: The immune consequences of trauma . Surg Clin North Am 1982;62:167-182. 3. Nohr CW, Christou NV, Rode H, et al: In vivo and in vitro humoral immunity in surgical patients . Ann Surg 1984;200:373-380.Crossref 4. Superina R, Meakins JL: Delayed hypersensitivity, anergy, and the surgical patient . J Surg Res 1984;37:151-174.Crossref 5. Wang BS, Heacock EH, Wu AVO, et al: Generation of suppressor cells in mice after surgical trauma . J Clin Invest 1980;66:200-209.Crossref 6. Lundy J, Ford CM: Surgery, trauma, and immune suppression: Evolving the mechanism . Ann Surg 1983;197:434-438.Crossref 7. Meakins JL, Pietsch JB, Bubenick O, et al: Delayed hypersensitivity: Indicator of acquired failure of host defenses in sepsis and trauma . Ann Surg 1977;186:241-250.Crossref 8. Pietsch JB, Meakins JL, Cotto D, et al: Delayed hypersensitivity responses: The effect of surgery . J Surg Res 1977;22:228-230.Crossref 9. Meakins JL, McLean AP, Kelly R, et al: Delayed hypersensitivity and neutrophil chemotaxis: Effect of trauma . J Trauma 1978;18:240-247.Crossref 10. Buffone V, Meakins JL, Christou NV: Neutrophil function in surgical patients: Relationship to adequate bacterial defenses . Arch Surg 1984;119: 39-43.Crossref 11. Allgower M, Durig M, Wolff G: Infection and trauma . Surg Clin North Am 1980;60:133-144. 12. Reinherz EL, Schlossman SF: Regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings . N Engl J Med 1980;303:370-373.Crossref 13. Kung PC, Goldstein G, Reinherz EL, et al: Monoclonal antibodies defining distinctive human T-cell surface antigens . Science 1979;206:347-349.Crossref 14. Lehmann PF, Gibbons J, Senitzer D, et al: T-lymphocyte abnormalities in disseminated histoplasmosis . Am J Med 1983;75:790-794.Crossref 15. Williams RC, Koster FT, Kilpatrick KA: Alterations in lymphocyte cell surface markers during various human infections . Am J Med 1983;75: 807-816.Crossref 16. Antonacci AC, Good RA, Gupta S: T-cell subpopulations following thermal injury . Surg Gynecol Obstet 1982;155:1-8. 17. Zapata-Sirvent RL, Hansbrough JF: Postburn immunosuppression in an animal model: III. Maintenance of normal helper and suppressor lymphocyte subpopulations by immunomodulating drugs . Surgery 1985;97: 721-727. 18. Hansbrough JF, Peterson V, Kortz E, et al: Postburn immunosuppression in an animal model: Monocyte dysfunction induced by burned tissue . Surgery 1983;93:415-423. 19. Howard RJ, Simmons RL: Acquired immunologic defects after trauma and surgical procedures . Surg Gynecol Obstet 1974;139:771-782. 20. Nohr CW, Christou NV, Rode H, et al: In vivo and in vitro humoral immunity in surgical patients . Ann Surg 1984;200:373-380.Crossref 21. Buffone V, Meakins JL,Christou NV: Neutrophil function in surgical patients: Relationship to adequate bacterial defenses . Arch Surg 1984;119: 39-43.Crossref 22. Deitch EA, Gelder F, McDonald JC: Sequential prospective analysis of the nonspecific host defense system after thermal injury . Arch Surg 1984;119:83-89.Crossref 23. Saba TM, Diluzio NR: Surgical stress and reticuloendothelial function . Surgery 1968;65:802-807. 24. Hansbrough JF, Bender EM, Zapata-Sirvent R, et al: Altered helper and suppressor lymphocyte populations in surgical patients: A measure of post-operative immunosuppression . Am J Surg 1984;148:303-307.Crossref 25. Johnson WC, Ulrich F, Muguid MM, et al: Role of delayed hypersensitivity in predicting postoperative morbidity and mortality . Am J Surg 1979;137:536-542.Crossref 26. Keane RM, Birmingham W, Shatney CM, et al: Prediction of sepsis in the multitraumatic patient by assays of lymphocyte responsiveness . Surg Gynecol Obstet 1983;156:163-167. 27. McLaughlin GA, Wu AV, Saporoschetz I, et al: Correlation between anergy and a circulating immunosuppressive factor following major surgical trauma . Ann Surg 1979;190:297-304.Crossref 28. Hansbrough JF, Peterson V, Zapata-Sirvent R, et al: Postburn immunosuppression in an animal model: II. Restoration of immunity by immunomodulating drugs . Surgery 1984;95:290-295. 29. Bohnen JM, Christou NV, Chiasson L, et al: Anergy secondary to sepsis in rats: Relation to outcome . Arch Surg 1984;119:117-120.Crossref 30. Rocklin RE, Bendtzen K, Greineder D: Mediators of immunity: Lymphokines and monokines . Adv Immunol 1980;29:55-127. 31. Payne J, Hayden P, Meyer HJ, et al: Observed differences in postoperative lymphocyte transformation are explained by patient and population variations . Am J Surg 1984;147:237-242.Crossref 32. Boudet RA, Morse PA, Watts LM: An analysis of human peripheral lymphocytes to phytohemagglutinin lymphoblastogenesis in whole blood . Surg Gynecol Obstet 1978;146:609-616. 33. Graybill JR, Alford RH: Variability of sequential studies of lymphocyte blastogenesis in normal adults . Clin Exp Immunol 1976;25:28-35. 34. Gershon RK, Leibhaver SA, Ryn S: T-cell regulation of T-cell responses to antigen . Immunology 1974;26:909-923. 35. Reinherz EL, Schlossman SF: Regulation of the immune response-inducer and suppressor T-lymphocyte subsets in human beings . N Engl J Med 1980;303:370-373.Crossref 36. Munster AM: Post-traumatic immunosuppression is due to activation of suppressor cells . Lancet 1976;1:1329.Crossref 37. Wood JJ, Rodrick ML, O'Mahony JB, et al: Inadequate interleukin production: A fundamental immunological deficiency in patients with major burns . Ann Surg 1984;200:311-320.Crossref 38. Beer DJ, Matloff SM, Rocklin RE: The influence of histamine on immune and inflammatory responses . Adv Immunol 1984;35:209-268. 39. Griswold DE, Alessi S, Badger AM, et al: Inhibition of suppressor cell expression by histamine type (H2) receptor antagonists . J Immunol 1984;132:3054-3057. 40. Goodwin JS: Immunologic effects of nonsteroidal anti-inflammatory drugs . Am J Med 1981;70:7-15.Crossref 41. Webb DR, Osheroff PL: Antigen stimulation of prostaglandin synthesis and control of immune responses . Proc Natl Acad Sci USA 1976;73: 1300-1309.Crossref 42. Askenase PW, Hayden BJ, Gershon RK: Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses . J Exp Med 1975;141:697-702.Crossref 43. Gill HK, Liew FY: Regulation of DTH-effect of cyclophosphamide on suppressor cells for DTH to sheep red blood cells in mice . Eur J Immunol 1978;8:172-176.Crossref 44. Schwartz A, Askenase PW, Gershon RK: Regulation of DTH reactions by cyclophosphamide-sensitive T cells . J Immunol 1978;121:1573-1577. 45. Kupper TS, Green DR, Chaudry IH, et al: A cyclophosphamide-sensitive T cell circuit induced by thermal injury . Surgery 1984;95:699-705. 46. Bender EM, Hansbrough JF, Zapata-Sirvent R, et al: Restoration of immunity in burned mice by cimetidine . J Trauma 1985;25:131-137.Crossref 47. Gershon RK, Eardley DD, Durum S, et al: Contrasuppression: A novel immunoregulatory activity . J Exp Med 1981;153:1533-1546.Crossref 48. Swain SL, Dutton RW: Mouse T-lymphocyte sub-populations: Relationships between function and Lyt antigen phenotype , in Inglis JR (ed): T Lymphocytes Today . New York, Elsevier Science Publishing Co Inc, 1983.

Journal

Archives of SurgeryAmerican Medical Association

Published: Jan 1, 1986

References