Dominance of T-helper 2-type cytokines after severe injury

V. E. Mack, M. D. McCarter, H. A. Naama, S. E. Calvano and J. M. Daly
Department of Surgery, New York Hospital-Cornell University Medical Center, New York, USA.

OBJECTIVE: To determine whether severe injury leads to a dominance of splenocyte-produced T-helper (Th) 2-type cytokines, partly explaining the observed defects in cellular immune responses in the posttraumatic state. DESIGN: Female BALB/c mice (n = 6 per group) were randomized to receive anesthesia alone (control) or a combined femur fracture and a hemorrhage of 40% of total blood volume (trauma). On days 1 and 7 after injury, mice were killed and spleens were harvested. Splenocytes were stimulated in vitro with 2.5 micrograms of concanavalin A per milliliter. After 72 hours of incubation, splenocyte proliferation was determined by means of tritiated thymidine uptake. Production of interferon-gamma and interleukins (IL) -2, -4, -5, -6, and -10 from supernatants harvested after 24 or 72 hours of incubation was quantified by enzyme-linked immunosorbent assay. SETTING: Surgical immunology research laboratory of a medical college. MAIN OUTCOME MEASURES: Mouse spleen weight, splenocyte number, and proliferation in addition to cytokine production (interferon-gamma, IL-2, IL-4, IL-5, IL-6, and IL-10). RESULTS: Splenocyte proliferative capacity was unaffected at day 1 after injury but was significantly suppressed (P < .05) by day 7 after injury. Similarly, there were no changes in splenocyte cytokine production in a comparison of control and injured mice at day 1. At day 7, however, there was nearly a 90% decrease in the Th1-type cytokines (interferon-gamma and IL-2; P < or = .002) and at least a 30% increase in the Th2-type cytokines IL-4, IL-5, IL-6, and IL-10 (P = .06 for IL-6 and P < or = .03 for IL-4, IL-5, and IL-10). CONCLUSIONS: These data indicate that a shift to a Th2-type splenocyte cytokine response occurs late, at 7 days after injury. Modulation of Th cell cytokine responses may partially explain defects observed in cellular immune responses in postinjury states. Therapies that augment Th1-type cytokine production and/or neutralize Th2-type cytokines may prove beneficial.

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