Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis

Plasma IL-6 levels of wild-type and knockout mice and correlation with mortality. (A) Plasma levels of IL-6 were determined 6 h after the onset of sepsis induced with a 21-gauge needle. All the wild-type mice had significant levels of IL-6 within the plasma, while in the knockout mice levels were nearly undetectable. Each value is the mean ± the standard error of the mean for nine mice, * = P <0.05. (B) Mice were divided into those with IL-6 levels greater than 3,000 pg/ml (n = 18) or less than 3,000 pg/ml (n = 33). Mice with higher levels of plasma IL-6 had significantly greater mortality, particularly in early phases of sepsis. P = 0.014 comparing the curves by log rank survival analysis.

Change in body weight 24 h prior to death. Mice were weighed daily, and the data are displayed as the change in body weight on the day prior to death. Since statistical analysis showed that a group effect (wild type versus knockout) was not present, the data were combined. There is a significant increase in the body weight of the mice that would die within the next 24 h compared to those mice that would live in the first 2 days. This difference became less apparent as the sepsis evolved. The value beneath each bar indicates the number of animals in that group. * = P <0.05 comparing mice that lived versus those that died.

Daily body weight following nonlethal cecal ligation and puncture. Mice were subjected to nonlethal 25-gauge single-puncture CLP. The IL-6KO mice had significantly less loss of body weight compared to the wild-type mice. There was a significant effect based on the day, as well as differences between the groups. Each value is the mean ± the standard error of the mean for 18 to 31 mice. * = P <0.05 (wild type compared to KO with Bonferroni correction).

Daily food consumption. The amount of food consumed each day was determined in 25-gauge single-puncture mice to match the data in Fig. 4. There is virtually no difference in the consumption of food between the wild-type and knockout mice, with the single exception of the day 3, when the knockout mice consumed more food. Each value is the mean ± the standard error of the mean for 18 to 31 mice.

Gross motor activity. Gross motor activity was determined using implanted radio transmitters. There is a rapid return to the normal diurnal variation in both the sham-operated and the 25-gauge single-puncture septic animals. In contrast, 25-gauge double-puncture animals essentially never regain normal diurnal variation. The light-dark bars indicate when the lights were on or off in the room. Each line is the mean of two to four mice.