Research Article
Stephan Dueren, Koroush Kabir,
Abstract
Pathogen associated microbial patterns (PAMP) such as lipopolysaccharides (LPS) and CpGoligodeoxynucleotides (CpG-ODN) are recognized by innate immunity via pattern recognition receptors (PRR), e.g. Toll-like receptors (TLR). Most of them involve recruitment of the adaptor molecule myeloid differentiation factor 88 (MyD88) followed by initiation of the ongoing signaling pathway. Preliminary studies demonstrated that CpG-ODN application induces cross-tolerance to LPS treatment in vitro. The present study investigated whether ODN containing CpG motifs could induce hyporesponsiveness following LPS treatment and reduce mortality. Interleukin (IL)-6 was determined in bronchoalveolar lavage (BAL) fluid as well lung histopathological changes. In total, 188 male Sprague-Dawley rats were randomly assigned to the following groups: In a first series, mortality was observed. To that end, animals received CpG-ODN or control-ODN i.p. (12 or 48 nmol) 8 hours, respectively 7 days prior to the bolus administration of i.p. endotoxin (25 mg/kg (=LD80) E. coli 0111:B4 LPS). Animals were monitored 7 days for mortality. In a second series, rats were treated with 12 nmol CpG-ODN or control-ODN i.p. 8 hours, respectively 7 days prior to the i.p. bolus administration of endotoxin (10 mg/kg (=LD0)). 3, 12 and 36 hours after LPS administration blood samples were drawn for blood cell counts. Organs were harvested, weighed and examined histopathologically. The BAL IL-6 levels were determined by ELISA. Mortality in the CpG-ODN treated groups was not significantly different from control-ODN groups. Blood cell counts, lung wet weight and histopathology of different organs did not show any different effects between CpG-ODN and control-ODN. No significant differences in BAL IL-6 levels between the groups could be demonstrated. In conclusion, positive in vitro data could not be transferred to a rat model of endotoxemia.