PMID- 9637160
OWN - NLM
STAT- MEDLINE
DCOM- 19980702
LR  - 20220317
IS  - 0022-5282 (Print)
IS  - 0022-5282 (Linking)
VI  - 44
IP  - 6
DP  - 1998 Jun
TI  - Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma 
      anergy.
PG  - 1037-45; discussion 1045-6
AB  - 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 associated with 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 
      an excess of immunosuppressive T LK (i.e., interleukin (IL)-10) but rather 
      results from lost T-cell regulatory networking. METHODS: Purified T cells from 37 
      severely injured trauma patients were cultured and stimulated with 
      alphaCD3/alphaCD4, and proliferation was assessed at 72 hours. Anergy is defined 
      as occurring when the patient's T-cell proliferation to alphaCD3/alphaCD4 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 was measured 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-10, 16.9%) 
      compared with increased or unchanged T LK production during the nonanergic state 
      (IL-2, 83%; IFNgamma, 230%; IL-4, 110%; and IL-10, 307.9%; p < 0.01). There was a 
      significant direct correlation between depressed IL-4 and depressed IFNgamma (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 also 
      specifically 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.
FAU - Puyana, J C
AU  - Puyana JC
AD  - Department of Surgery, University of Massachusetts Medical Center, Worcester, 
      USA.
FAU - Pellegrini, J D
AU  - Pellegrini JD
FAU - De, A K
AU  - De AK
FAU - Kodys, K
AU  - Kodys K
FAU - Silva, W E
AU  - Silva WE
FAU - Miller, C L
AU  - Miller CL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Trauma
JT  - The Journal of trauma
JID - 0376373
RN  - 0 (Interleukin-2)
RN  - 0 (Lymphokines)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Clonal Anergy/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Inflammation/immunology
MH  - Injury Severity Score
MH  - Interferon-gamma/immunology
MH  - Interleukin-10/immunology
MH  - Interleukin-2/immunology
MH  - Interleukin-4/immunology
MH  - Lymphokines/*immunology
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes/*immunology
MH  - Wounds and Injuries/*immunology
EDAT- 1998/06/24 00:00
MHDA- 1998/06/24 00:01
CRDT- 1998/06/24 00:00
PHST- 1998/06/24 00:00 [pubmed]
PHST- 1998/06/24 00:01 [medline]
PHST- 1998/06/24 00:00 [entrez]
AID - 10.1097/00005373-199806000-00017 [doi]
PST - ppublish
SO  - J Trauma. 1998 Jun;44(6):1037-45; discussion 1045-6. doi: 
      10.1097/00005373-199806000-00017.