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Canadian journal of veterinary research = Revue canadienne de recherche veterinaire1992; 56(2); 110-114;

Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002.

Abstract: The purpose of this study was to determine if a structurally novel dual inhibitor of arachidonic acid metabolism, SK & F 86002, would inhibit the endotoxin-induced production of tumor necrosis factor (TNF) activity by equine peritoneal macrophages. Equine peritoneal macrophages were variously pretreated for 0, 0.5 and 2 h with SK & F 86002 at 10(-9) to 10(-4) molar final concentrations or were left untreated. Then, the macrophages were cultured in vitro in the presence of endotoxin (5 ng/mL). Supernatant media were collected after 4 h and stored at -70 degrees C until assayed for TNF activity and immunoreactive thromboxane B2 (iTxB2). Macrophage supernatant TNF activities were estimated by an in vitro cytotoxicity bioassay using the murine fibrosarcoma cell line, WEHI 164 clone 13. Concentrations of iTxB2 were quantitated by radioimmunoassay. Coincubation of macrophages with SK & F 86002 significantly decreased the subsequent supernatant TNF activity. Concentrations of SK & F 86002 from 10(-7) to 10(-4) molar effectively reduced TNF production when added to macrophages 0 and 0.5 h prior to endotoxin. After 2 h of preincubation, SK & F 86002 significantly reduced supernatant TNF activity at 10(-5) and 10(-4) M concentrations. Supernatant concentrations of iTxB2 were reduced when SK & F 86002 was added at 10(-6) to 10(-4) M concentrations, 0 and 0.5 h prior to endotoxin, and at all concentrations (10(-9) to 10(-4)) when preincubated with macrophages for 2 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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Publication Date: 1992-04-01 PubMed ID: 1591653PubMed Central: PMC1263517
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explored how the compound SK & F 86002 can impact the production of tumor necrosis factor (TNF) in horse peritoneal macrophages. Specifically, they found that SK & F 86002 was able to significantly decrease TNF release, an important immune response, when macrophages were exposed to endotoxin in controlled conditions.

Research Aim and Methodology

  • The study aimed to ascertain if a newly formulated dual-inhibitor of arachidonic acid metabolism named SK & F 86002 could restrain the production of tumor necrosis factor (TNF) due to exposure to endotoxin in equine peritoneal macrophages.
  • Equine peritoneal macrophages were subjected to treatments involving SK & F 86002 for varying durations (0, 0.5, and 2 hours). The molar concentration of the inhibitor ranged between 10(-9) to 10(-4).
  • After treatment, these macrophages were cultured in vitro, in an environment consisting of endotoxin.
  • The supernatant media (the clear liquid left after precipitates have been removed) was obtained post 4 hours of culture and was stored at a temperature of -70 degrees Celsius for future TNF activity assays and immunoreactive thromboxane B2 (iTxB2) measurement.

Results of the Study

  • When SK & F 86002 was used in the process, the TNF activity in the supernatant was notably decreased, indicating a suppression of the immune response.
  • The inhibitor was most effective in minimizing TNF production when used 0 and 0.5 hours prior to the introduction of endotoxin, at concentrations ranging from 10(-7) to 10(-4) molar.
  • If the preincubation period was extended to 2 hours, SK & F 86002 could still significantly reduce TNF activity, albeit only at higher concentrations (10(-5) and 10(-4) M).
  • The substance also had an impact on iTxB2 concentrations. Direct contact of SK & F 86002 with the macrophages could reduce iTxB2 levels at concentrations from 10(-6) to 10(-4) M for 0 and 0.5 hours prior to endotoxin, whereas all concentrations led to reduced iTxB2 at 2 hours of preincubation.

Conclusion of the Study

  • The study strongly suggests that the compound SK & F 86002 effectively inhibits the production of tumor necrosis factor in macrophages, and this inhibitory effect is heightened when the macrophages are pre-treated with the compound prior to the introduction of endotoxin.
  • The research on SK & F 86002 may open new doors in controlling inflammatory responses in biological systems, particularly in reducing tumor necrosis factor activity, which is involved in systemic inflammation.

Cite This Article

APA
Morris DD, Crowe N, Moore JN. (1992). Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002. Can J Vet Res, 56(2), 110-114.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 56
Issue: 2
Pages: 110-114

Researcher Affiliations

Morris, D D
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602.
Crowe, N
    Moore, J N

      MeSH Terms

      • Animals
      • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
      • Arachidonic Acids / antagonists & inhibitors
      • Arachidonic Acids / metabolism
      • Cells, Cultured
      • Female
      • Horses
      • Imidazoles / pharmacology
      • Lipopolysaccharides / toxicity
      • Macrophages / drug effects
      • Macrophages / metabolism
      • Male
      • Peritoneal Cavity / cytology
      • Thiazoles / pharmacology
      • Tumor Necrosis Factor-alpha / biosynthesis

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