Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients

Zoltan Spolarics, Muhammad Siddiqi, John H. Siegel, Zenaida C. Garcia, Dana S. Stein, Thomas Denny, Edwin A. Deitch

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Objective: To determine the effect of major trauma on the cytokine-producing activity of monocytes and CD4+ T cells in a homogeneous cohort of patients as well as to determine the relationship between monocyte and T-lymphocyte responses and clinical outcome. Settings: Surgical intensive care units of a trauma center and flow cytometry and experimental laboratories at a teaching hospital. Design: Prospective cohort clinical study with measurements of white cell cytokine-producing activity on days 2, 5, and 10 postinjury. The number of cytokine-producing CD14+ monocytes, CD4+, and CD8+ T cells were determined in whole blood using flow cytometry combined with the intracellular cytokine staining method. Basal and lipopolysaccharide-stimulated interleukin (IL)-12, tumor necrosis factor-α, IL-6, and IL-1α production by monocytes as well as basal and phorbol 12-myristate 13-acetate plus ionomycin-stimulated interferon-γ, IL-4, and tumor necrosis factor-α production by T cells were determined on days 2, 5, and 10 postinjury and compared with similar measurements made in healthy control subjects. Patients: Twelve randomly selected black, male patients were enrolled in the study: mean injury severity score, 26; mean age, 35 yrs; mean Glasgow Coma Scale score, 13; systemic inflammatory response syndrome, 92%; sepsis, 42%; bronchial infection, 42%; and adult respiratory distress syndrome 25%. Main Results: After lipopolysaccharide stimulation, the number of IL-12-, tumor necrosis factor-α-, IL-1α-, and IL-6-producing CD14+ monocytes was 40% to 70% lower in trauma patients on postinjury days 2, 5, and 10 than in healthy control subjects. After phorbol 12-myristate 13-acetate stimulation, the number of IL-4-producing CD4+ cells increased three-fold in the trauma patients compared with healthy control subjects. In contrast, the number of interteron-γ- or tumor necrosis factor-α-producing CD4+ and CD8+ T cells was not different between the patients and control subjects. The Th1/Th2 ratio was significantly lower in patients on all postinjury days than in the control subjects. A statistically significant inverse correlation was found between the number of IL-12-producing monocytes and IL-4-producing CD4+ T cells in trauma patients (p = .007, r2 = .47). This correlation was absent in control subjects. The degree of depressed capacity of monocyte IL-12 production on day 2 postinjury showed a statistically significant correlation with the development of adult respiratory distress syndrome, sepsis, or infections and also with the duration of systemic inflammatory response syndrome and sepsis. Conclusions: Major trauma results in an early and marked decrease in monocyte cytokine-producing activity. The trauma-induced depression in IL-12 production by the mononuclear phagocyte system may promote T-cell commitment toward a Th2 pattern early after trauma. The appearance of the Th2 pattern is the result of elevated numbers of IL-4-producing cells without major alterations in T-cell interteron-γ-producing capacity. The degree of alterations in monocyte and T-cell responses on day 2 postinjury correlates with the development of adverse clinical outcomes and the subsequent duration of the inflammatory response.

Original languageEnglish (US)
Pages (from-to)1722-1729
Number of pages8
JournalCritical care medicine
Issue number6
StatePublished - Jun 1 2003

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

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