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Depression of cell-mediated immunity in patients following severe traumatic injury has been well documented in vitro and in vivo. However, the exact mechanism of this defect is still controversial. In this study, we have investigated the ability of injured patients' peripheral blood mononuclear cells (PBMC) to produce two important immunoregulatory molecules, interleukin 1 (IL 1) and interleukin 2 (IL 2). Eighteen traumatic injury patients were studied during the course of their hospital stay and their results compared with a group of 18 normal age- and sex-matched controls. The results showed the following. (1) Production of IL 2 by normal PBMC in response to optimal doses of mitogen may vary with sex as well as age. (2) Adherent mononuclear cells from trauma patients produced at least as much IL 1 as normals. (3) IL 2 production, however, was markedly suppressed (normals, 1.6 +/- 0.2 U; traumatic injury, 0.6 +/- 0.1 U; P = 0.001) and persisted for as long as 50 days postinjury. OKT4+ cells were not significantly decreased at any time, nor were OKT8+ suppressor/cytotoxic cells increased at any time. Decreased IL 2 production in patients treated with steroids or those who were septic was not different from that in those patients who were not treated with steroids or were not septic. These results suggest that the cause of the defect in IL 2 production in traumatic injury patients is not related to a lack of the IL 1 signal, producer T cells, or Ia+ monocytes or to increased suppressor T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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We studied the production of the two major mediators of cellular immune responses, Interleukin 1 (IL-1) and Interleukin 2 (IL-2), by the peripheral blood mononuclear cells of 23 burn patients (16 men, seven women, mean age 48.9 years) compared with 23 matched controls (16 men, seven women, mean age 46.7 years). Serial measurements were made of IL-1 production by adherent mononuclear cells after stimulation with lipopolysaccharide and of IL-2 production by lymphocytes after stimulation with phytohemagglutinin (PHA). Eighty determinations of IL-2 production by lymphocytes from 12 patients with greater than 30% body surface area burn revealed a mean IL-2 production of 0.71 u as compared with a mean of 1.23 u for patients with less than 30% burns (p = 0.04). Patients with greater than 30% body surface area burns had significantly reduced IL-2 production (p less than or equal to 0.05) until 60 days after injury, whereas those with smaller burns had reduced IL-2 production only at 20-29 and 30-39 days postburn. Nine burn patients with systemic sepsis showed significantly lower IL-2 production (p = 0.03) at 10-29 days postburn than nonseptic patients, and significantly less IL-2 production during septic episodes. Eight patients with greater than 50% suppression of lymphocyte response to PHA produced less IL-2 (0.4 u) than patients with less than 50% suppression, (1.07 u, p = 0.004). IL-1 production was significantly elevated as compared with controls (4.45 u vs. 3.6 u, p = 0.05) early after injury, but was subsequently within the normal range regardless of burn size. The percentage of circulating helper T-lymphocytes, the principal source of IL-2, was also reduced, although this did not always correlate with IL-2 production, which remained depressed after recovery of the helper T-cell population. These results indicate that failure to produce IL-2, a powerful mediator of cellular immune responses, is an important mechanism underlying the defective cell mediated immunity seen in burn patients.

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