Browsing by Subject "maksavaurio"

Idiosyncratic drug reaction denotes a non-immunological hypersensitivity to a substance unrelated to drug toxicity. Idiosyncratic drug reactions occur rarely and unpredictably amongst drug users. Endotoxins (lipopolysaccharides) are a part of the outer membrane of the cell wall of Gram-negative bacteria. Endotoxins may cause fever, leukopenia, and shock depending on the bacterial species and the health of the infected person. Usually endotoxins first insult the liver, a key detoxication organ in the host. Endotoxins can provoke Kuppfer cells to release pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin-1 (IL-1), which can lead to systemic inflammatory response and damage liver. Inflammation and liver damage can sensitize to idiosyncratic drug reactions. Endotoxin tolerance is defined as a reduced responsiveness to a lipopolysaccharide (LPS) challenge following the first encounter with endotoxin. Endotoxin tolerance is associated with a reduction of tumor necrosis factor alpha and interleukin-1 production in response to LPS. Endotoxin tolerance protects against a lethal challenge of LPS and prevents infection-inflicted tissue damage. The aim of this study was to determine such a dose and time-point after exposure which lead to a mild liver lesion and to increased hepatic levels of TNF-α and IL-1 mRNA in rats. We also made an attempt to induce endotoxin tolerance. 38 laboratory rats were used and studied in three rat groups. TNF-α and IL-1 levels were analyzed from rats killed 1, 3, 6, 12 or 24 h after endotoxin (1.0 mg/kg) given intraperitoneally. Endotoxin treatment resulted in significantly increased levels of TNF- α:n and IL-1 mRNA in all endotoxin-treated rats. Serum ASAT and ALAT levels also increased at 24 h. These results are consistent with tissue damage and inflammation in the liver. We failed to induce a clear endotoxin tolerance. The dose used (0,5 mg/kg) dose may have been too large for that.