Immunomodulatory intervention in sepsis by multidrug-resistant Pseudomonas aeruginosa with thalidomide: an experimental study.
BACKGROUND
Thalidomide is an inhibitor of tumour necrosis factor-alpha (TNFalpha) that has been proven effective for the treatment of experimental sepsis by Escherichia coli. It was tested whether it might behave as an effective immunomodulator in experimental sepsis by multidrug-resistant (MDR) Pseudomonas aeruginosa.


METHODS
Sepsis was induced by the intraperitoneal injection of 1 x 10(8) cfu/kg inoculum of the test isolate in a total of 10(9) Wistar rats divided in three groups as follows: group A controls; group B administered seed oil 30 minutes before bacterial challenge; and group C administered 50 mg/kg of thalidomide diluted in seed oil 30 minutes before bacterial challenge. Blood was sampled for estimation of endotoxins (LPS), TNFalpha, interferon-gamma (IFNgamma), nitric oxide (NO) and malondialdehyde (MDA). LPS was measured by the QCL-1000 LAL assay, TNFalpha and IFNgamma by ELISA, NO by a colorimetric assay and MDA by the thiobarbiturate assay.


RESULTS
Mean (+/- SE) survival of groups A, B and C were 18.60 +/- 1.84, 12.60 +/- 0.60 and 30.50 +/- 6.62 hours (p of comparisons A to C equal to 0.043 and B to C equal to 0.002). Decreased TNFalpha and NO levels were found in sera of animals of group C compared to group A. Plasma levels of LPS, MDA and IFNgamma did not differ between groups.


CONCLUSIONS
Intake of thalidomide considerably prolonged survival in experimental sepsis by MDR P. aeruginosa an effect probably attributed to decrease of serum TNFalpha.
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. giamarel@internet.gr
Evangelos J
EJ
Giamarellos-Bourboulis
Nikolaos
N
Bolanos
George
G
Laoutaris
Vassilios
V
Papadakis
Vassilios
V
Koussoulas
Despina
D
Perrea
Panayotis E
PE
Karayannacos
Helen
H
Giamarellou
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004731:Endotoxins / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy*; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D013792:Thalidomide; D007371:Interferon-gamma