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Role of Interleukin 6 and Transforming Growth Factor–β in the Induction of Depressed Splenocyte Responses Following Sepsis

Role of Interleukin 6 and Transforming Growth Factor–β in the Induction of Depressed Splenocyte... Abstract • We examined whether (1) there is an association between elevated circulating levels of transforming growth factor–β (TGF-β) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-β release) or TGF-β could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-β value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-β (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-β at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-β, thereby attenuating host immunosuppression during sepsis. (Arch Surg. 1993;128:89-95) References 1. Massague J. The transforming growth factor-β family . Ann Rev Cell Biol . 1990;6:597-641.Crossref 2. Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-β Immunol Today . 1989;10:258-261.Crossref 3. Wahl JS, Hunt DA, Wakefield LM, et al. Transforming growth factor type β induces monocyte chemotaxis and growth factor production . Proc Natl Acad Sci USA . 1987;84:5788-5792.Crossref 4. Kehrl JH, Wakefield LM, Roberts AB, et al. Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth . J Exp Med . 1986;163:1037-1050.Crossref 5. Wahl SM, Hunt DA, Bansal G, McCartney-Francis N, Ellingsworth L, Allen JB. Bacterial cell wall-induced immunosuppression: role of transforming growth factor β J Exp Med . 1988;168:1403-1417.Crossref 6. Miller-Graziano CL, Szabo G, Griffey K, Metha B, Kodys K, Catalano D. Role of elevated monocyte transforming growth factor beta (TGF-β) production in posttrauma immunosuppression . J Clin Immunol . 1991;11:95-102.Crossref 7. Zhou D, Munster AM, Winchurch RA. Inhibitory effects of interleukin 6 on immunity: possible implications in burn patients . Arch Surg . 1992;127: 65-69.Crossref 8. Zhou D, Munster A, Winchurch RA. Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-β . FASEB J . 1991;5:2582-2585. 9. Baker CC, Chaudry IH, Gaines HO, Baue AE. Evaluation of factors affecting mortality rate after sepsis in murine cecal ligation and puncture model . Surgery . 1983;94:331-335. 10. Ayala A, Kisala JM, Felt JA, Perrin MM, Chaudry IH. Does endotoxin tolerance prevent the release of inflammatory monokines (IL-1, IL-6, or TNF) during sepsis? Arch Surg . 1992;127:191-197.Crossref 11. Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J. B cell growth and differentiation activity of interleukin-HP1 and related murine plasmocytoma growth factors . Eur J Immunol . 1988;18:607-612.Crossref 12. Meldrum DR, Ayala A, Perrin MM, Ertel W, Chaudry IH. Diltiazem restores IL-2, IL-3, IL-6 and IFN-gamma synthesis and decreases susceptibility to sepsis following hemorrhage . J Surg Res . 1991;51:158-164.Crossref 13. Mishell BB, Shiigi SM. Selected Methods in Cellular Immunology . New York, NY: WH Freeman & Co; 1980:182-185. 14. Ayala A, Perrin MM, Chaudry IH. Defective macrophage antigen presentation following hemorrhage is associated with the loss of MHC class II (la) antigens . Immunology . 1990;70:33-39. 15. Van Snick J, Cayphas S, Vink A, et al. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas . Proc Natl Acad Sci U S A . 1986;83:9679-9683.Crossref 16. Cheifetz S, Weatherbee JA, Tsang ML-S, et al. The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors . Cell . 1987;48:409-415.Crossref 17. Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH. Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin . Cytokine . 1990;2:170-174.Crossref 18. Mizel SB. Production and quantitation of lymphocyte activating factor(interleukin 1) . In: Herscowitz HB, Holden HT, Bellanti JA, Ghaffar A, eds. Manual of Macrophage Methodology . New York, NY: Marcel Dekker Inc; 1981;407-441. 19. Ayala A, Perrin MM, Kisala JM, Ertel W, Chaudry IH. Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophage to release inflammatory mediators (IL-1, IL-6 and TNF) . Circ Shock . 1992;36:191-199. 20. Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T. The complex pattern of cytokines in serum from patients with meningococcal septic shock: association between interleukin 6, interleukin 1, and fatal outcome . J Exp Med . 1989;169:333-338.Crossref 21. Marano MA, Fong Y, Moldawer LL, et al. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality . Surg Gynecol Obstet . 1990;170:32-38. 22. Marks JD, Marks CB, Luce JM, et al. Plasma tumor necrosis factor in patients with septic shock . Am Rev Respir Dis . 1990;141:94-97.Crossref 23. Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans . Crit Care Med . 1989;17:975-978.Crossref 24. Stephan RN, Saizawa M, Conrad PJ, Dean RE, Geha AS, Chaudry IH. Depressed antigen presentation function and membrane interleukin-1 activity of peritoneal macrophages after laparotomy . Surgery . 1987;102:147-154. 25. Walker C, Kristensen F, Bettens F, DeWeck AL. Lymphokine regulation of activated (G1) lymphocytes: prostaglandin E2-induced inhibition of interleukin 2 production . J Immunol . 1983;130:1770-1773. 26. Grbic JT, Mannick JA, Gough DB, Rodrick ML. The role of prostaglandin E2 in immune suppression following injury . Ann Surg . 1991;214:253-263.Crossref 27. Miller CL, Fink MP, Wu JY, Sabo G, Kodys K. Mechanisms of altered monocyte prostaglandin E2 production in severely injured patients . Arch Surg . 1988;123:293-299.Crossref 28. Faist E, Mewes A, Baker CC, et al. Prostaglandin E, dependent suppression of interleukin-2 production in patients with major trauma . J Trauma . 1987;27:837-848.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Role of Interleukin 6 and Transforming Growth Factor–β in the Induction of Depressed Splenocyte Responses Following Sepsis

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Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1993.01420130101015
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Abstract

Abstract • We examined whether (1) there is an association between elevated circulating levels of transforming growth factor–β (TGF-β) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-β release) or TGF-β could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-β value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-β (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-β at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-β, thereby attenuating host immunosuppression during sepsis. (Arch Surg. 1993;128:89-95) References 1. Massague J. The transforming growth factor-β family . Ann Rev Cell Biol . 1990;6:597-641.Crossref 2. Wahl SM, McCartney-Francis N, Mergenhagen SE. Inflammatory and immunomodulatory roles of TGF-β Immunol Today . 1989;10:258-261.Crossref 3. Wahl JS, Hunt DA, Wakefield LM, et al. Transforming growth factor type β induces monocyte chemotaxis and growth factor production . Proc Natl Acad Sci USA . 1987;84:5788-5792.Crossref 4. Kehrl JH, Wakefield LM, Roberts AB, et al. Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth . J Exp Med . 1986;163:1037-1050.Crossref 5. Wahl SM, Hunt DA, Bansal G, McCartney-Francis N, Ellingsworth L, Allen JB. Bacterial cell wall-induced immunosuppression: role of transforming growth factor β J Exp Med . 1988;168:1403-1417.Crossref 6. Miller-Graziano CL, Szabo G, Griffey K, Metha B, Kodys K, Catalano D. Role of elevated monocyte transforming growth factor beta (TGF-β) production in posttrauma immunosuppression . J Clin Immunol . 1991;11:95-102.Crossref 7. Zhou D, Munster AM, Winchurch RA. Inhibitory effects of interleukin 6 on immunity: possible implications in burn patients . Arch Surg . 1992;127: 65-69.Crossref 8. Zhou D, Munster A, Winchurch RA. Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF-β . FASEB J . 1991;5:2582-2585. 9. Baker CC, Chaudry IH, Gaines HO, Baue AE. Evaluation of factors affecting mortality rate after sepsis in murine cecal ligation and puncture model . Surgery . 1983;94:331-335. 10. Ayala A, Kisala JM, Felt JA, Perrin MM, Chaudry IH. Does endotoxin tolerance prevent the release of inflammatory monokines (IL-1, IL-6, or TNF) during sepsis? Arch Surg . 1992;127:191-197.Crossref 11. Vink A, Coulie PG, Wauters P, Nordan RP, Van Snick J. B cell growth and differentiation activity of interleukin-HP1 and related murine plasmocytoma growth factors . Eur J Immunol . 1988;18:607-612.Crossref 12. Meldrum DR, Ayala A, Perrin MM, Ertel W, Chaudry IH. Diltiazem restores IL-2, IL-3, IL-6 and IFN-gamma synthesis and decreases susceptibility to sepsis following hemorrhage . J Surg Res . 1991;51:158-164.Crossref 13. Mishell BB, Shiigi SM. Selected Methods in Cellular Immunology . New York, NY: WH Freeman & Co; 1980:182-185. 14. Ayala A, Perrin MM, Chaudry IH. Defective macrophage antigen presentation following hemorrhage is associated with the loss of MHC class II (la) antigens . Immunology . 1990;70:33-39. 15. Van Snick J, Cayphas S, Vink A, et al. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas . Proc Natl Acad Sci U S A . 1986;83:9679-9683.Crossref 16. Cheifetz S, Weatherbee JA, Tsang ML-S, et al. The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors . Cell . 1987;48:409-415.Crossref 17. Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH. Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin . Cytokine . 1990;2:170-174.Crossref 18. Mizel SB. Production and quantitation of lymphocyte activating factor(interleukin 1) . In: Herscowitz HB, Holden HT, Bellanti JA, Ghaffar A, eds. Manual of Macrophage Methodology . New York, NY: Marcel Dekker Inc; 1981;407-441. 19. Ayala A, Perrin MM, Kisala JM, Ertel W, Chaudry IH. Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophage to release inflammatory mediators (IL-1, IL-6 and TNF) . Circ Shock . 1992;36:191-199. 20. Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T. The complex pattern of cytokines in serum from patients with meningococcal septic shock: association between interleukin 6, interleukin 1, and fatal outcome . J Exp Med . 1989;169:333-338.Crossref 21. Marano MA, Fong Y, Moldawer LL, et al. Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality . Surg Gynecol Obstet . 1990;170:32-38. 22. Marks JD, Marks CB, Luce JM, et al. Plasma tumor necrosis factor in patients with septic shock . Am Rev Respir Dis . 1990;141:94-97.Crossref 23. Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans . Crit Care Med . 1989;17:975-978.Crossref 24. Stephan RN, Saizawa M, Conrad PJ, Dean RE, Geha AS, Chaudry IH. Depressed antigen presentation function and membrane interleukin-1 activity of peritoneal macrophages after laparotomy . Surgery . 1987;102:147-154. 25. Walker C, Kristensen F, Bettens F, DeWeck AL. Lymphokine regulation of activated (G1) lymphocytes: prostaglandin E2-induced inhibition of interleukin 2 production . J Immunol . 1983;130:1770-1773. 26. Grbic JT, Mannick JA, Gough DB, Rodrick ML. The role of prostaglandin E2 in immune suppression following injury . Ann Surg . 1991;214:253-263.Crossref 27. Miller CL, Fink MP, Wu JY, Sabo G, Kodys K. Mechanisms of altered monocyte prostaglandin E2 production in severely injured patients . Arch Surg . 1988;123:293-299.Crossref 28. Faist E, Mewes A, Baker CC, et al. Prostaglandin E, dependent suppression of interleukin-2 production in patients with major trauma . J Trauma . 1987;27:837-848.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Jan 1, 1993

References