Skip to main content
Top
Published in: BMC Immunology 1/2010

Open Access 01-12-2010 | Research article

Divergent adaptive and innate immunological responses are observed in humans following blunt trauma

Authors: Kevin R Kasten, Holly S Goetzman, Maria R Reid, Alison M Rasper, Samuel G Adediran, Chad T Robinson, Cindy M Cave, Joseph S Solomkin, Alex B Lentsch, Jay A Johannigman, Charles C Caldwell

Published in: BMC Immunology | Issue 1/2010

Login to get access

Abstract

Background

The immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.

Results

Neutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.

Conclusions

These results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.
Appendix
Available only for authorised users
Literature
1.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3B.CrossRefPubMed Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3B.CrossRefPubMed
2.
go back to reference Murphy TJ, Paterson HM, Mannick JA, Lederer JA: Injury, sepsis, and the regulation of Toll-like receptor responses. J Leukoc Biol. 2004, 75: 400-407. 10.1189/jlb.0503233.CrossRefPubMed Murphy TJ, Paterson HM, Mannick JA, Lederer JA: Injury, sepsis, and the regulation of Toll-like receptor responses. J Leukoc Biol. 2004, 75: 400-407. 10.1189/jlb.0503233.CrossRefPubMed
3.
go back to reference Botha AJ, Moore FA, Moore EE, Kim FJ, Banerjee A, Peterson VM: Postinjury neutrophil priming and activation: an early vulnerable window. Surgery. 1995, 118: 358-364. 10.1016/S0039-6060(05)80345-9. discussion 364-355CrossRefPubMed Botha AJ, Moore FA, Moore EE, Kim FJ, Banerjee A, Peterson VM: Postinjury neutrophil priming and activation: an early vulnerable window. Surgery. 1995, 118: 358-364. 10.1016/S0039-6060(05)80345-9. discussion 364-355CrossRefPubMed
4.
go back to reference Partrick DA, Moore FA, Moore EE, Barnett CC, Silliman CC: Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horiz. 1996, 4: 194-210.PubMed Partrick DA, Moore FA, Moore EE, Barnett CC, Silliman CC: Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horiz. 1996, 4: 194-210.PubMed
5.
go back to reference Moore EE, Moore FA, Franciose RJ, Kim FJ, Biffl WL, Banerjee A: The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma. 1994, 37: 881-887. 10.1097/00005373-199412000-00002.CrossRefPubMed Moore EE, Moore FA, Franciose RJ, Kim FJ, Biffl WL, Banerjee A: The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma. 1994, 37: 881-887. 10.1097/00005373-199412000-00002.CrossRefPubMed
6.
go back to reference Remijsen Q, Berghe Vanden T, Parthoens E, Asselbergh B, Vandenabeele P, Willems J: Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt. J Leukoc Biol. 2009, 85: 497-507. 10.1189/jlb.0908525.CrossRefPubMed Remijsen Q, Berghe Vanden T, Parthoens E, Asselbergh B, Vandenabeele P, Willems J: Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt. J Leukoc Biol. 2009, 85: 497-507. 10.1189/jlb.0908525.CrossRefPubMed
7.
go back to reference Solomkin JS, Robinson CT, Cave CM, Ehmer B, Lentsch AB: Alterations in membrane cholesterol cause mobilization of lipid rafts from specific granules and prime human neutrophils for enhanced adherence-dependent oxidant production. Shock. 2007, 28: 334-338. 10.1097/shk.0b013e318047b893.CrossRefPubMed Solomkin JS, Robinson CT, Cave CM, Ehmer B, Lentsch AB: Alterations in membrane cholesterol cause mobilization of lipid rafts from specific granules and prime human neutrophils for enhanced adherence-dependent oxidant production. Shock. 2007, 28: 334-338. 10.1097/shk.0b013e318047b893.CrossRefPubMed
8.
9.
go back to reference Bandyopadhyay G, De A, Laudanski K, Li F, Lentz C, Bankey P, Miller-Graziano C: Negative signaling contributes to T-cell anergy in trauma patients. Crit Care Med. 2007, 35: 794-801. 10.1097/01.CCM.0000256847.61085.A5.CrossRefPubMed Bandyopadhyay G, De A, Laudanski K, Li F, Lentz C, Bankey P, Miller-Graziano C: Negative signaling contributes to T-cell anergy in trauma patients. Crit Care Med. 2007, 35: 794-801. 10.1097/01.CCM.0000256847.61085.A5.CrossRefPubMed
10.
go back to reference Cheadle WG, Pemberton RM, Robinson D, Livingston DH, Rodriguez JL, Polk HC: Lymphocyte subset responses to trauma and sepsis. J Trauma. 1993, 35: 844-849. 10.1097/00005373-199312000-00007.CrossRefPubMed Cheadle WG, Pemberton RM, Robinson D, Livingston DH, Rodriguez JL, Polk HC: Lymphocyte subset responses to trauma and sepsis. J Trauma. 1993, 35: 844-849. 10.1097/00005373-199312000-00007.CrossRefPubMed
11.
go back to reference Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999, 27: 1230-1251. 10.1097/00003246-199907000-00002.CrossRefPubMed Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE: Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999, 27: 1230-1251. 10.1097/00003246-199907000-00002.CrossRefPubMed
12.
go back to reference Adams CL, Grierson AM, Mowat AM, Harnett MM, Garside P: Differences in the kinetics, amplitude, and localization of ERK activation in anergy and priming revealed at the level of individual primary T cells by laser scanning cytometry. J Immunol. 2004, 173: 1579-1586.CrossRefPubMed Adams CL, Grierson AM, Mowat AM, Harnett MM, Garside P: Differences in the kinetics, amplitude, and localization of ERK activation in anergy and priming revealed at the level of individual primary T cells by laser scanning cytometry. J Immunol. 2004, 173: 1579-1586.CrossRefPubMed
13.
go back to reference Faist E, Schinkel C, Zimmer S, Kremer JP, Von Donnersmarck GH, Schildberg FW: Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signalling. J Trauma. 1993, 34: 846-853. 10.1097/00005373-199306000-00014. discussion 853-844CrossRefPubMed Faist E, Schinkel C, Zimmer S, Kremer JP, Von Donnersmarck GH, Schildberg FW: Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signalling. J Trauma. 1993, 34: 846-853. 10.1097/00005373-199306000-00014. discussion 853-844CrossRefPubMed
14.
go back to reference Spolarics Z, Siddiqi M, Siegel JH, Garcia ZC, Stein DS, Denny T, Deitch EA: Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients. Crit Care Med. 2003, 31: 1722-1729. 10.1097/01.CCM.0000063579.43470.AA.CrossRefPubMed Spolarics Z, Siddiqi M, Siegel JH, Garcia ZC, Stein DS, Denny T, Deitch EA: Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients. Crit Care Med. 2003, 31: 1722-1729. 10.1097/01.CCM.0000063579.43470.AA.CrossRefPubMed
15.
go back to reference Rajan G, Sleigh JW: Lymphocyte counts and the development of nosocomial sepsis. Intensive Care Med. 1997, 23: 1187-10.1007/s001340050482.CrossRefPubMed Rajan G, Sleigh JW: Lymphocyte counts and the development of nosocomial sepsis. Intensive Care Med. 1997, 23: 1187-10.1007/s001340050482.CrossRefPubMed
16.
go back to reference Cross AS, Opal SM: A new paradigm for the treatment of sepsis: is it time to consider combination therapy?. Ann Intern Med. 2003, 138: 502-505.CrossRefPubMed Cross AS, Opal SM: A new paradigm for the treatment of sepsis: is it time to consider combination therapy?. Ann Intern Med. 2003, 138: 502-505.CrossRefPubMed
17.
go back to reference Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG, Sitkovsky MV: Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol. 2001, 167: 6140-6149.CrossRefPubMed Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG, Sitkovsky MV: Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol. 2001, 167: 6140-6149.CrossRefPubMed
18.
go back to reference Foulds KE, Wu CY, Seder RA: Th1 memory: implications for vaccine development. Immunol Rev. 2006, 211: 58-66. 10.1111/j.0105-2896.2006.00400.x.CrossRefPubMed Foulds KE, Wu CY, Seder RA: Th1 memory: implications for vaccine development. Immunol Rev. 2006, 211: 58-66. 10.1111/j.0105-2896.2006.00400.x.CrossRefPubMed
19.
go back to reference Nathan CF, Murray HW, Wiebe ME, Rubin BY: Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983, 158: 670-689. 10.1084/jem.158.3.670.CrossRefPubMed Nathan CF, Murray HW, Wiebe ME, Rubin BY: Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983, 158: 670-689. 10.1084/jem.158.3.670.CrossRefPubMed
20.
go back to reference Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, Karl IE: Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001, 166: 6952-6963.CrossRefPubMed Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, Karl IE: Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001, 166: 6952-6963.CrossRefPubMed
21.
go back to reference Wesche DE, Lomas-Neira JL, Perl M, Chung CS, Ayala A: Leukocyte apoptosis and its significance in sepsis and shock. J Leukoc Biol. 2005, 78: 325-337. 10.1189/jlb.0105017.CrossRefPubMed Wesche DE, Lomas-Neira JL, Perl M, Chung CS, Ayala A: Leukocyte apoptosis and its significance in sepsis and shock. J Leukoc Biol. 2005, 78: 325-337. 10.1189/jlb.0105017.CrossRefPubMed
22.
go back to reference Kurosaka K, Watanabe N, Kobayashi Y: Potentiation by human serum of anti-inflammatory cytokine production by human macrophages in response to apoptotic cells. J Leukoc Biol. 2002, 71: 950-956.PubMed Kurosaka K, Watanabe N, Kobayashi Y: Potentiation by human serum of anti-inflammatory cytokine production by human macrophages in response to apoptotic cells. J Leukoc Biol. 2002, 71: 950-956.PubMed
23.
go back to reference Lipniacki T, Hat B, Faeder JR, Hlavacek WS: Stochastic effects and bistability in T cell receptor signaling. J Theor Biol. 2008, 254: 110-122. 10.1016/j.jtbi.2008.05.001.PubMedCentralCrossRefPubMed Lipniacki T, Hat B, Faeder JR, Hlavacek WS: Stochastic effects and bistability in T cell receptor signaling. J Theor Biol. 2008, 254: 110-122. 10.1016/j.jtbi.2008.05.001.PubMedCentralCrossRefPubMed
24.
go back to reference Laudanski K, Miller-Graziano C, Xiao W, Mindrinos MN, Richards DR, De A, Moldawer LL, Maier RV, Bankey P, Baker HV, et al.,: Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci USA. 2006, 103: 15564-15569. 10.1073/pnas.0607028103.PubMedCentralCrossRefPubMed Laudanski K, Miller-Graziano C, Xiao W, Mindrinos MN, Richards DR, De A, Moldawer LL, Maier RV, Bankey P, Baker HV, et al.,: Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci USA. 2006, 103: 15564-15569. 10.1073/pnas.0607028103.PubMedCentralCrossRefPubMed
25.
go back to reference Chen Q, Powell DW, Rane MJ, Singh S, Butt W, Klein JB, McLeish KR: Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J Immunol. 2003, 170: 5302-5308.CrossRefPubMed Chen Q, Powell DW, Rane MJ, Singh S, Butt W, Klein JB, McLeish KR: Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J Immunol. 2003, 170: 5302-5308.CrossRefPubMed
26.
go back to reference Hu Z, Sayeed MM: Activation of PI3-kinase/PKB contributes to delay in neutrophil apoptosis after thermal injury. Am J Physiol Cell Physiol. 2005, 288: C1171-1178. 10.1152/ajpcell.00312.2004.CrossRefPubMed Hu Z, Sayeed MM: Activation of PI3-kinase/PKB contributes to delay in neutrophil apoptosis after thermal injury. Am J Physiol Cell Physiol. 2005, 288: C1171-1178. 10.1152/ajpcell.00312.2004.CrossRefPubMed
27.
go back to reference Yang KY, Arcaroli JJ, Abraham E: Early alterations in neutrophil activation are associated with outcome in acute lung injury. Am J Respir Crit Care Med. 2003, 167: 1567-1574. 10.1164/rccm.200207-664OC.CrossRefPubMed Yang KY, Arcaroli JJ, Abraham E: Early alterations in neutrophil activation are associated with outcome in acute lung injury. Am J Respir Crit Care Med. 2003, 167: 1567-1574. 10.1164/rccm.200207-664OC.CrossRefPubMed
28.
go back to reference Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, et al.,: Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science. 1994, 263: 92-95. 10.1126/science.8272873.CrossRefPubMed Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, et al.,: Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science. 1994, 263: 92-95. 10.1126/science.8272873.CrossRefPubMed
29.
go back to reference Fuhrer DK, Yang YC: Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11. Biochem Biophys Res Commun. 1996, 224: 289-296. 10.1006/bbrc.1996.1023.CrossRefPubMed Fuhrer DK, Yang YC: Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11. Biochem Biophys Res Commun. 1996, 224: 289-296. 10.1006/bbrc.1996.1023.CrossRefPubMed
30.
go back to reference Janssens V, Longin S, Goris J: PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail). Trends Biochem Sci. 2008, 33: 113-121.CrossRefPubMed Janssens V, Longin S, Goris J: PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail). Trends Biochem Sci. 2008, 33: 113-121.CrossRefPubMed
31.
go back to reference Millward TA, Zolnierowicz S, Hemmings BA: Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci. 1999, 24: 186-191. 10.1016/S0968-0004(99)01375-4.CrossRefPubMed Millward TA, Zolnierowicz S, Hemmings BA: Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem Sci. 1999, 24: 186-191. 10.1016/S0968-0004(99)01375-4.CrossRefPubMed
Metadata
Title
Divergent adaptive and innate immunological responses are observed in humans following blunt trauma
Authors
Kevin R Kasten
Holly S Goetzman
Maria R Reid
Alison M Rasper
Samuel G Adediran
Chad T Robinson
Cindy M Cave
Joseph S Solomkin
Alex B Lentsch
Jay A Johannigman
Charles C Caldwell
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2010
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-11-4

Other articles of this Issue 1/2010

BMC Immunology 1/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.