Plasma cytokines following thermal injury and their relationship with patient mortality, burn size, and time postburn.

We measured plasma levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) following thermal injury. Cytokine levels in the plasma of 27 burned patients were serially screened by ELISA and compared with cytokine levels in 16 healthy laboratory employees. The relationships between cytokine concentrations and patient mortality, burn size, and time postburn were examined. Plasma samples with detectable amounts of IL-1 beta and IL-6 were significantly more frequent in burned patients than in controls, whereas TNF alpha was undetectable in most plasma samples. All nonsurviving burned patients had detectable IL-6 levels; these were significantly higher than those of surviving patients. The IL-1 beta and IL-6 concentrations were highest during the first week after injury and declined over time. The IL-1 beta concentrations were positively correlated with burn size. These findings suggest that IL-1 beta and IL-6 may influence metabolic and immunologic responses in the first few weeks following thermal injury. Tumor necrosis factor alpha was transiently elevated in a small subpopulation of burned patients with no obvious relationship to burn size or time postburn.

Plasma cytokines after thermal injury and their relationship to infection.

OBJECTIVE: The relationship of plasma cytokine levels to infection, core temperature, and to one another in patients with thermal injury was examined. SUMMARY BACKGROUND DATA: The response to infection has been associated with cytokines such as interleukin 1 beta (IL1 beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF alpha), and these cytokines have been studied in various inflammatory diseases. The authors previously reported that patients with thermal injury have elevated IL1 beta and IL6 plasma levels and that these cytokines may play different roles in the response to thermal injury. METHODS: IL1 beta, IL6, and TNF alpha were measured by enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 27 patients. RESULTS: IL6 and TNF alpha levels were increased in severely infected patients as compared to patients who remained free of infection, and the IL6 level was higher in infected patients who died than those who survived. There was no apparent relationship between IL1 beta levels and infection. IL6 and IL1 beta were positively correlated with core temperature. The correlations between IL6 and IL1 beta, between IL6 and TNF alpha, and between TNF alpha and IL1 beta were significant. CONCLUSIONS: These results suggest that IL6 and TNF alpha play a role in the response of burned patients to infection.

The effects of thermal injury on serum interleukin 1 activity in rats.

Interleukin 1 (IL-1) is present in the blood of burned patients but its pathophysiologic role is not fully understood. Rat models would be useful research tools, if this cytokine could be identified in a complex fluid like blood. We describe a methodology, which revealed IL-1 activity from the serum of burned rats. Serum was collected from 37 rats with 30% total body surface burns and 9 unburned controls. To vary the burn response, the wounds of 17 rats were seeded with nonvirulent Pseudomonas aeruginosa at the time of injury. IL-1 activity was assessed by its capacity to induce IL-2 secretion in murine lymphoma cells (LBRM-33-1A5). Only after the serum had been fractionated, concentrated, and dialyzed, was IL-1 activity uncovered. Sera from burned rats contained five times more IL-1 activity than those from control animals (p < 0.05). There was no difference in serum IL-1 activity between burned and burn-seeded animals. The IL-1 activity was heat labile, and not produced by P. aeruginosa endotoxin, TNF-alpha, or endogenous IL-2 in rat serum. These results confirm that serum IL-1 levels are increased following thermal injury, and that there is no apparent relationship between IL-1 levels and infection. The serum preparation scheme presented in this study offers a reasonable approach to the measurement of serum IL-1 levels in rat models of disease and injury.