Both T-Helper-1- and T-Helper-2-Type Lymphokines Are Depressed in Posttrauma Anergy

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Abstract
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. Purified T cells 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 was measured by the multiple organ dysfunction syndrome (MODS) and Acute Physiology and Chronic Health Evaluation III scores. 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%; IFN gamma, 230%; IL-4, 110%; and IL-10, 307.9%; p 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.