BOTH T-HELPER-1-TYPE AND T-HELPER-2-TYPE LYMPHOKINES ARE DEPRESSED INPOSTTRAUMA ANERGY

Background: We have previously shown that an intrinsic postinjury T-ce ll dysfunction defined as lack of proliferative response to direct sti mulation 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 immun osuppression and associated with poor patient outcome. Here, we hypoth esize 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 rathe r results from lost T-cell regulatory networking. Methods: Purified T cells from 37 severely injured trauma patients were cultured and stimu lated with alpha CD3/alpha CD4, and proliferation was assessed at 72 h ours. Anergy is defined as occurring when the patient's T-cell prolife ration to alpha CD3/alpha CD4 is less than 50% of the simultaneously r un normal proliferation. Culture supernatants were assessed for T LK p roduction by enzyme-linked immunosorbent assay. Clinical severity was measured by the multiple organ dysfunction syndrome (MODS) and Acute P hysiology and Chronic Health Evaluation III scores. Results: Anergy oc curred 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 producti on 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 LK production 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 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 s ignificantly higher (7.6) than their MODS score in the absence of aner gy (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/I L-2 ratio greater than 1, We found, however, that this ratio was not g reater 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 ly mphokine profile. Both depressed T-cell proliferation and depressed LK production correlate to poor clinical outcome.