Deficient Transforming Growth Factor Beta and Interleukin-10 Responses Contribute to the Septic Death of Burned Patients

In order to understand the roles of pro-inflammatory and anti-inflammatory cytokines in burn injury and sepsis post-burn, serial changes in serum levels of transforming growth factor beta-1 (TGF-beta-1) were determined and compared to those of IL-6 and IL-10 in 15 burned patients. Among these 15 patients, 8 recovered without sepsis. The other seven, who were septic, expired. Our results showed that an initial peak serum TGF-beta-1 response was detected within 1 day post-burn. Peak serum IL-6 and IL-10 responses were also detected within 4 days after the burn injury of these patients. Significant differences in peak serum IL-6, IL-10 and TGF-beta-1 levels were not found between patients with total body surface area (TBSA) of greater or less than 50% and between patients who survived or expired from burn injury. Afterwards, levels of circulating IL-6 and IL-10 remained low in the survivors. However, a second peak response in serum TGF-beta-1 levels was observed in all burned patients analyzed. The second peak serum TGF-beta-1 levels post-burn of the eight survivors and the seven non-survivors were from 28,542 to 76,554 pg/ml (a mean value of 51,256+/-14,264 pg/ml) and from 8616 to 40,851 pg/ml (a mean value of 24,079+/-10,399 pg/ml), respectively. A significant difference (P<0.01) in mean values of the second peak TGF-beta-1 responses between groups of survivors and non-survivors was detected. Levels of circulating IL-6 in the septic non-surviving patients showed a tendency to increase 1-2 weeks post-burn and reached high levels before the expiration of these patients. After an initial peak response, the serum IL-10 level remained low in one of the seven non-survivors, while it increased in the other six non-survivors. However, marked increases in circulating IL-10 levels were observed only just before the death of these non-survivors. In conclusion, an initial increase in serum levels of IL-6, IL-10 and TGF-beta-1 was detected post-burn. A marked increase in serum levels of IL-6 before death suggests its role in the pathophysiology of sepsis in burned patients. In addition, a low secondary TGF-beta-1 response and a lack and/or delay in the increase of circulating IL-10 in the non-survivors may all contribute to the pathophysiology of septic death in burned patients.