Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs

H. Nakamura, A. Ishizaka, T. Urano, K. Sayama, F. Sakamaki, T. Terashima, Y. Waki, Kenzo Soejima, S. Tasaka, Naoki Hasegawa, Seitaro Fujishima, M. Kanazawa

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Abstract

SDZ MRL 953 (SDZ), a novel immunostimulatory lipid A. analog, has been reported to have immunopharmacological activities similar to those of lipopolysaccharide (LPS) but to have little of the toxicity of LPS. We investigated the effects of pretreatment with SDZ on Escherichia coli endotoxin-induced acute lung injury in guinea pigs, Four experimental groups consisted of saline control (n = 16), SDZ (-12 h) plus LPS (2 mg/kg of SDZ per kg of body weight injected intravenously 12 h before intravenous injection of 2 mg of LPS per kg; 15), SDZ (-10 min) plus LPS (SDZ injected 10 min before LPS injection; n = 10), and LPS alone (It = 16). The animals were sacrificed, land lung tissue was sampled 4 h after LPS or saline infusion. Lung injury was assessed by measuring the wet weight-to-dry weight ratio and the level of 125I-labeled albumin accumulation in bronchoalveolar lavage fluid relative to that in plasma. In the SDZ (-12 h) plus LPS group, these two parameters of acute lung injury were decreased compared with those in the LPS alone group. However, they were not decreased in the SDZ (-10 min) plus LPS group. We conclude that SDZ attenuates endotoxin-induced acute lung injury when it Is administered 12 h before LPS injection. The attenuating effects of SDZ are Speculated to be due to down regulation of the response to endotoxin rather than to receptor blocking.

Original languageEnglish
Pages (from-to)672-677
Number of pages6
JournalClinical and Diagnostic Laboratory Immunology
Volume2
Issue number6
Publication statusPublished - 1995

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Lipid A
Acute Lung Injury
Endotoxins
Lipopolysaccharides
Guinea Pigs
SDZ MRL 953
Weights and Measures
Injections
Bronchoalveolar Lavage Fluid
Lung Injury
Intravenous Injections
Toxicity
Albumins
Animals
Down-Regulation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

Nakamura, H., Ishizaka, A., Urano, T., Sayama, K., Sakamaki, F., Terashima, T., ... Kanazawa, M. (1995). Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs. Clinical and Diagnostic Laboratory Immunology, 2(6), 672-677.

Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs. / Nakamura, H.; Ishizaka, A.; Urano, T.; Sayama, K.; Sakamaki, F.; Terashima, T.; Waki, Y.; Soejima, Kenzo; Tasaka, S.; Hasegawa, Naoki; Fujishima, Seitaro; Kanazawa, M.

In: Clinical and Diagnostic Laboratory Immunology, Vol. 2, No. 6, 1995, p. 672-677.

Research output: Contribution to journalArticle

Nakamura, H. ; Ishizaka, A. ; Urano, T. ; Sayama, K. ; Sakamaki, F. ; Terashima, T. ; Waki, Y. ; Soejima, Kenzo ; Tasaka, S. ; Hasegawa, Naoki ; Fujishima, Seitaro ; Kanazawa, M. / Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs. In: Clinical and Diagnostic Laboratory Immunology. 1995 ; Vol. 2, No. 6. pp. 672-677.
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