Abstract

It  is still an open question as to whether or not aseptic injuries affect  the generation of fever due to exogenous pyrogens including bacterial  products. Therefore, in the present paper we have investigated the  course of endotoxin fever in rats induced with lipopolysaccharide (LPS;  given intraperitoneally in a dose of 50 μg/kg) 48 h after subcutaneous  administration of turpentine oil (TRP; 0.1 mL per rat) that causes  aseptic necrosis of tissues. We found that febrile response was  significantly augmented in the animals pre-treated with turpentine  compared to control rats (pre-treated with saline), and that observed  excessive elevation of body temperature (Tb) was accompanied by enhanced  release of fever mediators: interleukin-6 (IL-6) and prostaglandin E2 (PGE2)  into plasma. Moreover, we found that sensitization to pyrogenic effects  of lipopolysaccharide was associated with the increase in plasma level  of high mobility group box 1 protein (HMGB1), one of the best-known  damage-associated molecular patterns (DAMP), which was recently  discovered as inflammatory mediator. Since the injection of anti-HMGB1  antibodies weakened observed hyperpyrexia in the animals pre-treated  with turpentine, we conclude that HMGB1 is a plasma-derived factor  released in the course of aseptic injury that enhances pyrogenic effects  of LPS.