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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 a was transiently elevated in a small subpopulation of burned patients with no obvious relationship to burn size or time postburn.

Clinical and laboratory studies during the past two decades have documented that changes in leukocyte number and function can represent both the causes and the effects of infection, sepsis, and injury in surgical patients. Injury elicits a response from the immune system that is proportional to the magnitude of the insult and causes impaired function in some cells while sensitizing other cells so that a second insult will trigger an exaggerated and prolonged response. The cytokines and other metabolic products of activated leukocytes are also recognized as mixed blessings which, depending on magnitude and time of production, can act either beneficially to provide or enhance host resistance and thereby prevent or control infection, or deleteriously to depress the function of remote organs and cause systemic inflammation associated with cellular death and tissue injury.

Several fluorescent substances are present in the supernatants of acid precipitated whole blood or plasma from burned patients. Perchloric acid supernatants of sera from infected, but not uninfected, burned rats contained a fluorescent substance with maximum emission at 420 nm at 355-nm excitation (355 ex/420 em). In this study of serum from burned human patients, several fluorescent substances were resolved by reverse-phase high-pressure liquid chromatography. One of these fluorescent components had an high-pressure liquid chromatography retention time and fluorescent characteristics identical to those of neopterin. The identification of this component as neopterin was verified by thermospray mass spectrometry. Serum neopterin concentrations were then determined in supernatants of patient serum samples having various levels of 355 ex/420 em fluorescence. A correlation was found between the concentrations of neopterin determined by high-pressure liquid chromatography and the presence of bacteremia in burned patients. These findings suggest that neopterin, which is a useful indicator of infection In other clinical settings, may also be an indicator of infection in bumed patients.

Alterations in granulocyte function after thermal injury have been described. We have serially studied the level of granulocyte cytosolic peroxidase activity in 23 thermally injured patients during the first 6 weeks after injury. The patients' mean age and burn size were 35.1 + or - 15.7 years and 41.6% + or - 16.8% (range, 18% to 88%), respectively. Fourteen patients had concomitant inhalation injury, and the overall mortality rate was 4.3%.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

Pub. in Surgery, v108 n2 p172-178 Aug 90.

Increased infection rates in burned patients may result from a disproportionate increase in the suppressor subpopulations. Measurement of lymphocyte subpopulations is difficult in burned patients because gradient- purified cells are contaminated by nonlymphoid cells. The accuracy of flow cytometric subpopulation analysis was improved by restricting (gating) the analysis to cells with light scatter intensity typical of lymphocytes. Blood was obtained 48 hours after burn from rats receiving no burns, 30% scald burns, or burns seeded with Pseudomonas aeruginosa to induce infection. Subpopulations were identified by monoclonal antibodies to T-lymphocyte antigens. Gating increased the values obtained for most subpopulations, but the relative differences between groups were unchanged. Burned and infected animals, but not animals burned only, had a decreased ratio of helper to suppressor lymphocytes (HSR) relative to control. A decreased HSR relative to control. A decreased HSR correlated with sepsis, but not with infection susceptibility. This suggests that a decrease in HSR may be a result of infection rather than a cause of susceptibility to infection.