Submitted on March 30, 2007
Accepted on March 4, 2008
Intratracheal perfluorocarbons diminish LPS induced increase in systemic TNF
Wolfram Burkhardt1, Petra Koehne2, Heide Wissel3, Susanne Graf3, Hans Proquitte3, Roland R. Wauer3, and Mario Rudiger1*
1 Department for Neonatology and Pediatric Intensive Care Medicine, Klinik fur Kinderheilkunde; Universitatsklinikum C.G.Carus, Dresden, Germany
2 Clinic for Neonatology, Campus Virchow Klinikum, Charite Universitatsmedizin Berlin, Berlin, Germany
3 Clinic for Neonatology, Campus Mitte, Charite Universitatsmedizin Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: mario.ruediger{at}i-med.ac.at.
Perfluorocarbons (PFC) reduce the production of various inflammatory cytokines, including TNF
. The anti-inflammatory effect is not entirely understood. If anti-inflammatory properties are caused by a mechanical barrier, PFC in the alveoli should have no effect upon the inflammatory response to intravenous lipopopolysacharids (LPS) administration.
To test that hypothesis, rats (n=31) received LPS intravenously and were either spontaneously breathing (Spont), conventionally ventilated (CMV) or received partial liquid ventilation (PLV). Serum concentration of TNF was measured. The pulmonary expressions of TNF and TNF receptor 1 protein, and of TNF and ICAM-1 mRNA were determined.
LPS caused a significant (p<0.001) increase in serum TNF. Serum TNF concentration was similar in LPS/Spont (525 ±180 pg/ml) and LPS/CMV (504 ±154 pg/ml), but was significantly (p<0.001) lower in animals of the LPS/PLV-group (274 ±101 pg/ml). Immunhistochemical data on TNF protein expression showed a LPS-induced increase in TNF and TNFR1 expression, which was diminished by partial liquid ventilation. PCR measurements revealed a lower expression of TNF and ICAM-1 mRNA in LPS/PLV than in LPS/CMV or LPS/Spont animals. Semi-quantitative histological evaluation revealed only minor alveolar inflammation with no significant differences between the groups.
Low serum TNF concentration in PFC treated animals is most likely explained by a decreased production of TNF in the lung.
