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Titolo:
BOTH T-HELPER-1-TYPE AND T-HELPER-2-TYPE LYMPHOKINES ARE DEPRESSED INPOSTTRAUMA ANERGY
Autore:
PUYANA JC; PELLEGRINI JD; DE AK; KODYS K; SILVA WE; MILLER CL;
Indirizzi:
BRIGHAM & WOMENS HOSP,DEPT SURG,75 FRANCIS ST BOSTON MA 02115 UNIV MASSACHUSETTS,MED CTR,DEPT SURG WORCESTER MA 00000
Titolo Testata:
The journal of trauma, injury, infection, and critical care
fascicolo: 6, volume: 44, anno: 1998,
pagine: 1037 - 1045
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTERFERON-GAMMA; TRAUMA PATIENTS; HUMAN MONOCYTES; T-LYMPHOCYTES; SEPSIS; INTERLEUKIN-10; SUSCEPTIBILITY; CELLS; IL-10; MACROPHAGES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
J.C. Puyana et al., "BOTH T-HELPER-1-TYPE AND T-HELPER-2-TYPE LYMPHOKINES ARE DEPRESSED INPOSTTRAUMA ANERGY", The journal of trauma, injury, infection, and critical care, 44(6), 1998, pp. 1037-1045

Abstract

Background: We have previously shown that an intrinsic postinjury T-cell dysfunction defined as lack of proliferative response to direct stimulation through the T-cell receptor, referred to here as ''anergy,''occurs in a subgroup of patients with severe trauma and is associatedwith organ failure, It has been suggested recently that a dominance of T-helper-2 (Th2) lymphokine production might be responsible for immunosuppression and associated with poor patient outcome. Here, we hypothesize that anergy is associated with global failure of T lymphokine (T LK) production, suggesting that poor outcome is not the result of anexcess of immunosuppressive T LK (i.e., interleukin (IL)-10) but rather results from lost T-cell regulatory networking. Methods: Purified Tcells from 37 severely injured trauma patients were cultured and stimulated with alpha CD3/alpha CD4, and proliferation was assessed at 72 hours. Anergy is defined as occurring when the patient's T-cell proliferation to alpha CD3/alpha CD4 is less than 50% of the simultaneously run normal proliferation. Culture supernatants were assessed for T LK production by enzyme-linked immunosorbent assay. Clinical severity wasmeasured by the multiple organ dysfunction syndrome (MODS) and Acute Physiology and Chronic Health Evaluation III scores. Results: Anergy occurred in 20 of 37 patients, and it usually appeared at greater than 5 to 7 days after injury. There was a global reduction of T LK production during T-cell anergy (IL-2, 2.5%; interferon (IFN)gamma, 30.5%; IL-4, 11.8%; and IL-IO, 16.9%) compared with increased or unchanged T LKproduction during the nonanergic state (IL-2, 83%; IFN gamma, 230%; IL-4, 110%; and IL-10, 307.9%; p < 0.01), There was a significant direct correlation between depressed IL-4 and depressed IFN gamma (r = 0.620,p < 0.001), indicating a diminished LK production of both types of T-helper cells (Th1 and Th2). Decreased IL-2 and IL-10 levels were alsospecifically correlated to each other during the anergic state (r = 0.91,p < 0.001), The average MODS score for patients during anergy was significantly higher (7.6) than their MODS score in the absence of anergy (4.0, p = 0.01), When IL-2 and IL-10 were measured simultaneously,a predominance of Th2 LK (IL-10) production would result in an IL-10/IL-2 ratio greater than 1, We found, however, that this ratio was not greater than 1 in 80% of assays in which T cells were anergic (p = 0.01). Conclusion: During T-cell anergy there is not a predominance of Th2 lymphokine production but rather a global depression of the T-cell lymphokine profile. Both depressed T-cell proliferation and depressed LK production correlate to poor clinical outcome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 13:25:35