Ma. Rogy et al., PERSISTENTLY ELEVATED SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR AND INTERLEUKIN-1 RECEPTOR ANTAGONIST LEVELS IN CRITICALLY ILL PATIENTS, Journal of the American College of Surgeons, 178(2), 1994, pp. 132-138
The appearance of endogenously produced inhibitors against tumor necro
sis factor (TNF) (soluble TNF-receptor type I, sTNFR-I) and interleuki
n-l (IL-1 receptor antagonist, IL-1ra) was evaluated acutely in five n
ormal patients after experimental endotoxemia lipoplysaccharide (LPS)
and prospectively during a one to 11 week period in 12 septic, critica
lly ill patients. Increased levels of both factors remained detectable
in the circulation for up to 24 hours after LPS (2 nanograms per kilo
gram body weight) administration in normal patients. Despite free TNF-
a activity being detected only sporadically (3 percent of the samples)
and that IL-1 beta was never detectable in the patients in the intens
ive care unit, IL-6 bioactivity was present in 90 percent of initial s
amples. Circulating sTNFR-I levels up to 62,000 picograms per millilit
er and IL-1ra levels of 14,800 picograms per milliliter were noted in
the critically ill patients and remained consistently detectable throu
ghout the extended period of evaluation. While there was no difference
in IL-1ra levels between patients who survived or ultimately died, sT
NFR-I levels were significantly (p<0.001) lower in survivors compared
with nonsurvivors. A correlation between circulating sTNFR-I and concu
rrent cortisol levels (r=0.64; p<0.002) was also noted. Furthermore, a
correlation between sTNFR-I and the severity of initial insult, as as
sessed by APACHE II scores (r=0.54; p<0.01) was demonstrable. These na
turally occurring cytokine antagonists likely represent additional ind
icators of the presence of an infectious or other inflammatory process
and seem to persist in the circulation even during conditions in whic
h their respective proinflammatory cytokines are not demonstrable.