{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:08:10Z","timestamp":1762916890034},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,3,30]],"date-time":"2004-03-30T00:00:00Z","timestamp":1080604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3,30]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>Severe trauma can lead to a compromised immune response, thereby increasing susceptibility to infections. Here we will study to what extent these early changes in the immune status upon trauma affect a primary immune response to keyhole limpet haemocyanin (KLH). Because glutamine is the preferred respiratory substrate for immune competent cells and known to be depleted after trauma, we studied the immune status and the primary sensitization in relation to the glutamine plasma concentration in a group of severe trauma patients [injury severity score (ISS) &amp;gt;17]. Trauma patients (n\u2003=\u200331) were sensitized with KLH within 12 h after trauma; plasma glutamine concentrations and immune parameters were determined, after which KLH-specific immune responsiveness was evaluated on days 9 and 14. Low plasma glutamine concentrations were found after trauma. Significantly elevated numbers of granulocytes and CD14-positive leucocytes were found, whereas the HLA-DR expression on CD14-positive cells was significantly lower in trauma patients than in healthy controls. Trauma did not change the in vitro proliferative capacity of lymphocytes when cultured with glutamine; however, when lymphocytes were cultured without glutamine, trauma resulted in lower proliferation than healthy controls. Phytohaemagglutinin-(PHA)-induced interferon (IFN)-\u03b3 and interleukin (IL)-10 production was significantly lower after trauma, whereas IL-4 production was not affected. KLH sensitization following trauma resulted in poor skin test reactivity and low in vitro KLH-induced lymphocyte proliferation compared to controls. In contrast, the development of anti-KLH IgM, IgG, IgA, IgG1, IgG2, IgG3 and IgG4 production on days 9 and 14 following trauma was not different from that in healthy controls. Major trauma was associated with a reduced cell-mediated immune response, correlating with low plasma glutamine concentrations, while no effects of trauma were found on the development of a primary humoral immune response.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02447.x","type":"journal-article","created":{"date-parts":[[2004,4,8]],"date-time":"2004-04-08T08:00:40Z","timestamp":1081411240000},"page":"356-364","source":"Crossref","is-referenced-by-count":19,"title":["Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine"],"prefix":"10.1093","volume":"136","author":[{"given":"P G","family":"BOELENS","sequence":"first","affiliation":[{"name":"Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J C M","family":"FONK","sequence":"additional","affiliation":[{"name":"Department of Pathology of the VU University Medical Centre, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A P J","family":"HOUDIJK","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R J","family":"SCHEPER","sequence":"additional","affiliation":[{"name":"Department of Pathology of the VU University Medical Centre, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J T H M","family":"HAARMAN","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"MEIJER","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P A M","family":"VAN LEEUWEN","sequence":"additional","affiliation":[{"name":"Department of Surgery"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B M E","family":"VON BLOMBERG-VAN DER FLIER","sequence":"additional","affiliation":[{"name":"Department of Pathology of the VU University Medical Centre, Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,3,30]]},"reference":[{"key":"2022011223184589900_b1","doi-asserted-by":"crossref","first-page":"680","DOI":"10.7326\/0003-4819-125-8-199610150-00009","article-title":"Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS)","volume":"125","author":"Bone","year":"1996","journal-title":"Ann Intern Med"},{"key":"2022011223184589900_b2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0026-0495(88)90036-4","article-title":"Glutamine and glucose metabolism in human peripheral lymphocytes","volume":"37","author":"Ardawi","year":"1988","journal-title":"Metabolism"},{"key":"2022011223184589900_b3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0968-4328(99)00036-0","article-title":"Keyhole limpet hemocyanin (KLH): a biomedical review","volume":"30","author":"Harris","year":"1999","journal-title":"Micron"},{"key":"2022011223184589900_b4","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/00005373-197804000-00003","article-title":"Delayed hypersensitivity and neutrophil chemotaxis: effect of trauma","volume":"18","author":"Meakins","year":"1978","journal-title":"J Trauma"},{"key":"2022011223184589900_b5","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/archsurg.1982.01380340002002","article-title":"Anergy, immunosuppressive serum, and impaired lymphocyte blastogenesis in burn patients","volume":"117","author":"Wolfe","year":"1982","journal-title":"Arch Surg"},{"key":"2022011223184589900_b6","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/00000658-199522240-00011","article-title":"The delayed hypersensitivity response and host resistance in surgical patients: 20 years later","volume":"222","author":"Christou","year":"1995","journal-title":"Ann Surg"},{"key":"2022011223184589900_b7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/00000658-199902000-00013","article-title":"HLA-DR expression and soluble HLA-DR levels in septic patients after trauma","volume":"229","author":"Ditschkowski","year":"1999","journal-title":"Ann Surg"},{"key":"2022011223184589900_b8","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/bjs.1800770225","article-title":"Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patient","volume":"77","author":"Hershman","year":"1990","journal-title":"Br J Surg"},{"key":"2022011223184589900_b9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0140-6736(93)92303-B","article-title":"Biological variation in the development of sepsis after surgery or trauma","volume":"342","author":"Guillou","year":"1993","journal-title":"Lancet"},{"key":"2022011223184589900_b10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1378\/chest.104.3.847","article-title":"Altered leukocyte immunophenotypes in septic shock. Studies of HLA-DR, Cd11b, Cd14, and IL-2R expression","volume":"104","author":"Lin","year":"1993","journal-title":"Chest"},{"key":"2022011223184589900_b11","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1097\/00003246-199422100-00015","article-title":"Relationships between plasma cytokine concentrations and leukocyte functional antigen expression in patients with sepsis","volume":"22","author":"Lin","year":"1994","journal-title":"Crit Care Med"},{"key":"2022011223184589900_b12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/bjs.1800800224","article-title":"Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery","volume":"80","author":"Wakefield","year":"1993","journal-title":"Br J Surg"},{"key":"2022011223184589900_b13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1006\/clin.1996.4289","article-title":"Only a subset of trauma patients with depressed mitogen responses have true T cell dysfunctions","volume":"82","author":"De","year":"1997","journal-title":"Clin Immunol Immunopathol"},{"key":"2022011223184589900_b14","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0167-5699(96)80606-2","article-title":"The expanding universe of T-cell subsets: Th1, Th2 and more","volume":"17","author":"Mosmann","year":"1996","journal-title":"Immunol Today"},{"key":"2022011223184589900_b15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0039-6060(96)80118-8","article-title":"Surgical stress induces a shift in the type-1\/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma","volume":"119","author":"Decker","year":"1996","journal-title":"Surgery"},{"key":"2022011223184589900_b16","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1001\/archsurg.1996.01430240057007","article-title":"Dominance of T-helper 2-type cytokines after severe injury","volume":"131","author":"Mack","year":"1996","journal-title":"Arch Surg"},{"key":"2022011223184589900_b17","first-page":"145","article-title":"The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns","volume":"54","author":"Newsholme","year":"1987","journal-title":"Biochem Soc Symp"},{"key":"2022011223184589900_b18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/00005373-197403000-00001","article-title":"The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care","volume":"14","author":"Baker","year":"1974","journal-title":"J Trauma"},{"key":"2022011223184589900_b19","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0022-1759(84)90291-6","article-title":"Measurement of primary in vivo IgM- and IgG-antibody response to KLH in humans: implications of pre-immune IgM binding in antigen-specific ELISA","volume":"74","author":"Korver","year":"1984","journal-title":"J Immunol Meth"},{"key":"2022011223184589900_b20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/clinchem\/40.2.245","article-title":"Plasma amino acids determined by liquid chromatography within 17 minutes","volume":"40","author":"Teerlink","year":"1994","journal-title":"Clin Chem"},{"key":"2022011223184589900_b21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/00005373-197902000-00002","article-title":"Mononuclear cell analysis of peripheral blood from burn patients","volume":"19","author":"Volenec","year":"1979","journal-title":"J Trauma"},{"key":"2022011223184589900_b22","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1002\/eji.1830231213","article-title":"Phenotypical and functional characterization of Fc gamma receptor I (CD64)-negative monocytes, a minor human monocyte subpopulation with high accessory and antiviral activity","volume":"23","author":"Grage-Griebenow","year":"1993","journal-title":"Eur J Immunol"},{"key":"2022011223184589900_b23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1006\/cimm.1995.1181","article-title":"Modulation of MHC class II expression in human cells by dexamethasone","volume":"165","author":"Schwiebert","year":"1995","journal-title":"Cell Immunol"},{"key":"2022011223184589900_b24","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1182\/blood.V86.4.1564.bloodjournal8641564","article-title":"Influence of glutamine on the phenotype and function of human monocytes","volume":"86","author":"Spittler","year":"1995","journal-title":"Blood"},{"key":"2022011223184589900_b25","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1084\/jem.174.4.915","article-title":"Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression","volume":"174","author":"De Waal","year":"1991","journal-title":"J Exp Med"},{"key":"2022011223184589900_b26","first-page":"311","article-title":"IL-10 augments CD23 expression on U937 cells and down-regulates IL-4-driven CD23 expression on cultured human blood monocytes: effects of IL-10 and other cytokines on cell phenotype and phagocytosis","volume":"85","author":"Spittler","year":"1995","journal-title":"Immunology"},{"key":"2022011223184589900_b27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/archsurg.1997.01430280099016","article-title":"Interleukin-10. A role in the development of postoperative immunosuppression","volume":"132","author":"Klava","year":"1997","journal-title":"Arch Surg"},{"key":"2022011223184589900_b28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1054\/clnu.2000.0153","article-title":"Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes","volume":"20","author":"Spittler","year":"2001","journal-title":"Clin Nutr"},{"key":"2022011223184589900_b29","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1093\/jn\/132.9.2580","article-title":"Glutamine-enriched enteral nutrition increases HLA-DR expression on monocytes of trauma patients","volume":"132","author":"Boelens","year":"2002","journal-title":"J Nutr"},{"key":"2022011223184589900_b30","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1097\/00005373-199806000-00017","article-title":"Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma anergy","volume":"44","author":"Puyana","year":"1998","journal-title":"J Trauma"},{"key":"2022011223184589900_b31","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/00000658-199522240-00006","article-title":"Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection","volume":"222","author":"O'Sullivan","year":"1995","journal-title":"Ann Surg"},{"key":"2022011223184589900_b32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0002-9610(98)00299-2","article-title":"Downregulation of T helper type 1 immune response and altered pro-inflammatory and anti-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery","volume":"177","author":"Brune","year":"1999","journal-title":"Am J Surg"},{"key":"2022011223184589900_b33","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1097\/00005373-199705000-00018","article-title":"Postburn constitutional changes in T-cell reactivity occur in CD8+ rather than in CD4+ cells","volume":"42","author":"Zedler","year":"1997","journal-title":"J Trauma"},{"key":"2022011223184589900_b34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00003246-199901000-00028","article-title":"T-cell reactivity and its predictive role in immunosuppression after burns","volume":"27","author":"Zedler","year":"1999","journal-title":"Crit Care Med"},{"key":"2022011223184589900_b35","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1001\/archsurg.135.11.1309","article-title":"The potential pattern of circulating lymphocytes TH1\/TH2 is not altered after multiple injuries","volume":"135","author":"Wick","year":"2000","journal-title":"Arch Surg"},{"key":"2022011223184589900_b36","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1006\/clim.1999.4788","article-title":"Effect of glutamine on Th1 and Th2 cytokine responses of human peripheral blood mononuclear cells","volume":"93","author":"Chang","year":"1999","journal-title":"Clin Immunol"},{"key":"2022011223184589900_b37","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s002689900071","article-title":"Update on the mechanisms of immune suppression of injury and immune modulation","volume":"20","author":"Faist","year":"1996","journal-title":"World J Surg"},{"key":"2022011223184589900_b38","first-page":"442","article-title":"Induction of an immune response to keyhole-limpet hemocyanin in surgical patients with anergy","volume":"107","author":"Puyana","year":"1990","journal-title":"Surgery"},{"key":"2022011223184589900_b39","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1001\/archsurg.1989.01410120087017","article-title":"Dynamics of immunoglobulin synthesis after major trauma. Influence of recombinant lymphokines","volume":"124","author":"Ertel","year":"1989","journal-title":"Arch Surg"},{"key":"2022011223184589900_b40","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1097\/00005373-199005000-00011","article-title":"Immunologic defects following trauma: a delay in immunoglobulin synthesis by cultured B cells following traumatic accidents but not elective surgery","volume":"30","author":"Richter","year":"1990","journal-title":"J Trauma"},{"key":"2022011223184589900_b41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1001\/archsurg.1990.01410130097013","article-title":"Impaired antibody production in blunt trauma. Possible role for T cell dysfunction","volume":"125","author":"McRitchie","year":"1990","journal-title":"Arch Surg"},{"key":"2022011223184589900_b42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/archsurg.1991.01410260027004","article-title":"Humoral immunity in surgical patients with and without trauma","volume":"126","author":"Schneider","year":"1991","journal-title":"Arch Surg"},{"key":"2022011223184589900_b43","first-page":"229","article-title":"In vivo and in vitro humoral immunity in surgical patients: antibody response to pneumococcal polysaccharide","volume":"100","author":"Nohr","year":"1986","journal-title":"Surgery"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2004.02447.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/136\/2\/356\/42146703\/j.1365-2249.2004.02447.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/136\/2\/356\/42146703\/j.1365-2249.2004.02447.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T23:31:45Z","timestamp":1642030305000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/136\/2\/356\/6478837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,30]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2004,3,30]]},"published-print":{"date-parts":[[2004,3,30]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2004.02447.x","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,5]]},"published":{"date-parts":[[2004,3,30]]}}}