Intratracheal perfluorocarbons diminish LPS-induced increase in systemic TNF-alpha.
Perfluorocarbons (PFC) reduce the production of various inflammatory cytokines, including TNF-alpha. 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 on the inflammatory response to intravenous LPS administration. To test that hypothesis, rats (n=31) were administered LPS intravenously and were either spontaneously breathing (Spont), conventionally ventilated (CMV), or receiving partial liquid ventilation (PLV). Serum concentration of TNF-alpha was measured. The pulmonary expressions of TNF-alpha and TNF-alpha receptor 1 protein and of TNF-alpha and ICAM-1 mRNA were determined. LPS caused a significant (P<0.001) increase in serum TNF-alpha. Serum TNF-alpha 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). Immunohistochemical data on TNF-alpha protein expression showed a LPS-induced increase in TNF-alpha and TNF-alpha receptor 1 expression that was diminished by partial liquid ventilation. PCR measurements revealed a lower expression of TNF-alpha and ICAM-1 mRNA in LPS/PLV than in LPS/CMV or LPS/Spont animals. Semiquantitative histological evaluation revealed only minor alveolar inflammation with no significant differences between the groups. Low serum TNF-alpha concentration in PFC-treated animals is most likely explained by a decreased production of TNF-alpha in the lung.
Burkhardt
Wolfram
W
Dept. for Neonatology and Pediatric Intensive Care Medicine, Klinik für Kinderheilkunde, Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät der Technischen Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Koehne
Petra
P
Wissel
Heide
H
Graf
Susanne
S
Proquitté
Hans
H
Wauer
Roland R
RR
Rüdiger
Mario
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000494:pharmacology*; D016753:Interleukin-10 / Q000097:blood; D007385:Intermittent Positive-Pressure Ventilation; D008070:Lipopolysaccharides / Q000009:adverse effects; D021061:Liquid Ventilation; D008168:Lung / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013990:Tidal Volume / Q000187:drug effects; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005466:Fluorocarbons; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10