Dehydroxymethylepoxyquinomicin (DHMEQ) can suppress tumour necrosis factor-α production in lipopolysaccharide-injected mice, resulting in rescuing mice from death in vivo

Author:

Shimo T1,Adachi Y23,Umezawa K4,Okigaki M5,Takaya J1,Taniuchi S1,Ikehara S3,Kaneko K1

Affiliation:

1. Department of Pediatrics, Kansai Medical University, Moriguchi City, Osaka

2. Division of Clinical Pathology, Public Toyooka Hospital, Toyooka City, Hyogo

3. Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka

4. Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama City, Kanagawa

5. Department of Cardiovascular and Renal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan

Abstract

Summary Dehydroxymethylepoxyquinomicin (DHMEQ), a new nuclear factor (NF)-κB inhibitor, has several beneficial effects, including the suppression of tumour growth and anti-inflammatory effects. DHMEQ can also suppress the production of tumour necrosis factor (TNF)-α induced by lipopolysaccharide (LPS) in vitro. In the present study, we examine the effects of DHMEQ on TNF-α production in vivo and on the survival of mice injected with LPS. When DHMEQ was injected into mice 2 h before LPS injection, the survival of the LPS-injected mice was prolonged. When DHMEQ was injected twice (2 h before LPS injection and the day after LPS injection), all the mice were rescued. The injection of DHMEQ 1 h after LPS injection and the day after LPS injection also resulted in the rescue of all mice. The serum levels of TNF-α in the mice that received both LPS and DHMEQ were suppressed compared to the mice that received only LPS. These results suggest that DHMEQ can be utilized for the prevention and treatment of endotoxin shock.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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