Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma anergy.
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).


CONCLUSIONS
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.
Puyana
J C
JC
Department of Surgery, University of Massachusetts Medical Center, Worcester, USA.
Pellegrini
J D
JD
De
A K
AK
Kodys
K
K
Silva
W E
WE
Miller
C L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017635:Clonal Anergy / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015601:Injury Severity Score; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008222:Lymphokines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
D007376:Interleukin-2; D008222:Lymphokines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma