Effects of CpG motifs on mortality and lung inflammation in | 18234
International Research Journals

Effects of CpG motifs on mortality and lung inflammation in a rat model of endotoxemia


Stephan Dueren, Koroush Kabir, Lewis F. Neville, Eva Steinringer, Guido Grass, Micaela Mathiak, Peter Behrens, Christoph Rangger, Lutz Besch, Thomas Minor, and Guenther Mathiak

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.

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