A. Baykal et al., Epinephrine and endotoxin tolerance differentially modulate serum cytokinelevels to high-dose lipopolysaccharide challenge in a murine model, SURGERY, 125(4), 1999, pp. 403-410
Background. The epinephrine tolerance state has been demonstrated to increa
se survival in endotoxic shock and was claimed to have cross-tolerance with
endotoxin tolerance. With use of these data, we aimed to determine the eff
ect of epinephrine and endotoxin tolerance on major cytokine levels in a li
popolysaccharide challenge in mice.
Methods. Epinephrine tolerance was induced by beginning with a low dose and
gradually increasing to a lethal dose. Endotoxin tolerance was induced by
injecting saline solution for 4 days and lipopolysaccharide 1 mg/kg on the
fifth day. After these procedures, saline solution or 20 mg/kg lipopolysacc
haride was injected into animals. Peak serum levels of tumor necrosis facto
r-alpha (TNF-alpha), interleukin 1 beta, interleukin 6 (IL-6), interleukin
10 (IL-10), and interleukin 12 (IL-12) were assayed.
Results. The lipopolysaccharide injection increased the levels of all the c
ytokines in the control and epinephrine-tolerant animals. TNF-alpha, IL-6,
and IL-10 levels were lower in endotoxin-tolerant animals compared with con
trols. Epinephrine-tolerant animals had higher levels of TNF-alpha, IL-6, a
nd IL-12 than the controls did.
Conclusion. Epinephrine tolerance primes for an exaggerated release of TNF-
alpha, IL-6, and IL-12 in response to lipopolysaccharide challenge, suggest
ing anti-inflammatory and immunosuppressive effects by epinephrine. The ant
i-inflammatory effect was not mediated through increased IL-10 release. End
otoxin tolerance selectively modulated cytokine release.