Comparison of the efficacy of pentoxifylline and albifyllin (HWA 138) on endotoxin-induced cytokine production, coagulation disturbances, and mortality.
We have evaluated two different xanthine derivatives, pentoxifylline (POF) and albifyllin (HWA), in rat endotoxemia for their ability to reduce 1) cytokine formation, 2) coagulation disturbances, and 3) mortality. The animals were injected with lipopolysaccharide (LPS) (15 mg/kg i.p.) and received HWA or POF (25, 50, or 100 mg/kg) or saline 30 min before LPS administration. The plasma tumor necrosis factor levels were significantly reduced and in a similar manner by pretreatment with HWA or POF in vivo as well as in vitro. Neither the coagulation disturbance nor the characteristic leukopenia that follow an LPS challenge were significantly influenced by the xanthine derivatives. At a dose of 100 mg/kg, the 6 day mortality was significantly reduced by HWA to 36% but only attenuated by POF to 55% as compared to 80% in the control group. The similar effect of both agents on cytokine formation and coagulation disturbances indicate that, at least to a substantial degree, other mechanisms may account for the significant protection of rats against endotoxin-induced mortality by HWA only. HWA 138 may, therefore, be a new powerful agent against endotoxin-related disorders and mortality.
Bahrami
S
S
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Yao
Y M
YM
Shiga
H
H
Leichtfried
G
G
Redl
H
H
Schlag
G
G
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000009:adverse effects*; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001993:Bronchodilator Agents; D016207:Cytokines; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D000990:Antithrombin III; D010431:Pentoxifylline