Ethanol and LPS stimulation of ¹⁸F FHBG uptake by lung and heart of NF Kappa B TK transgenic mice

Objectives NF Kappa B (NF-κB) is a transcription factor that is intimately involved in acute and chronic inflammation. It has been suggested that ethanol administration blunts the stimulation of ¹⁸FDG uptake in vivo. In the present study we used a NF-κB reporter mouse in which the gene for viral thymidine kinase (TK) was introduced and is under the control of the same promoter as NF-κB and biodistribution with 9-[(4-[18F]fluoro)-3-hydroxymethylbutyl] guanine (¹⁸F FHBG) to quantitatively evaluate the effect of ethanol pretreatment on LPS stimulation of NF-κB expression.

Methods Male transgenic mice (28-30 grams) were fasted overnight. The mice were injected intraperitonealy with ethanol (5 g/kg, 20% vol/vol, in saline) or saline. 30 minutes later the mice were injected intravenously with LPS (33 mg/kg). One hour later the mice were injected with ¹⁸F FHBG, 5 microcurie/kg. One hour after that, the mice were sacrificed by carbon dioxide and subjected to complete necroscopy. Tissues were weighed and radioactivity was measured with a Wizard 1480 gamma counter. Results were expressed as %Dose/gram tissue, mean ± SD. There were six mice in each group.

Results Both LPS and ethanol injection into the NF-κB transgenic mouse resulted in significant increases in ¹⁸F FHBG uptake by lung (p<0.01) and heart (p<0.05). The combination of ethanol and LPS resulted in a greater increase in lung uptake of ¹⁸F FHBG than either treatment separately. However, the combined treatment did not effect ¹⁸F FHBG uptake compared to individual treatments.

Conclusions Conclusion: Ethanol pretreatment can enhance the alterations in NF-κB produced by LPS injection, in part, by altering NF-κB expression.

Research Support Shriners Hospital for Children, Bosto

• Download figure
• Open in new tab
• Download powerpoint

*p <0.05 compared to sham, **p<0.01 compared to sham