Vasopressin inhibits endotoxin-induced upregulation of inflammatory mediators in activated macrophages

Tsui-Chin Peng^{a, b}, Chun-Jen Huang^{a, b}

^a Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei, Taiwan
^b School of Medicine, Tzu Chi University, Hualien, Taiwan

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Abstract
Objectives

We sought to elucidate the effects of vasopressin on modulating the endotoxin-induced upregulation of inflammatory mediators.

Materials and Methods

A confluent murine macrophage-like cell line, RAW264.7 cells, were treated with lipopolysaccharide (LPS) (100 ng/mL) or with LPS plus vasopressin (10 pg/mL, 100 pg/mL, or 1000 pg/mL); the cells were denoted as the LPS group, the LPS-V(10) group, the LPS-V(100) group, and the LPS-V(1000) group, respectively. The respective control groups were run simultaneously. Vasopressin was administered immediately after LPS. The expression of inflammatory molecules was then assayed. The molecules that were assayed included the chemokine macrophage-inflammatory protein-2 (MIP-2); the cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); nitric oxide (NO)/inducible NO synthase (iNOS); and prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2).

Results

The differences between the LPS and LPS-V(10) groups in the concentration of inflammatory mediators were not statistically significant. By contrast, the LPS-V(100) and LPS-V(1000) groups were significantly lower than the LPS group in the concentration of MIP-2 (p = 0.004 and p = 0.001, respectively), TNF-α (p = 0.045 and p = 0.007, respectively), IL-1β (p = 0.003 and p < 0.001, respectively), NO (p = 0.014 and p = 0.001, respectively), iNOS mRNA (p = 0.001 and p < 0.001, respectively), PGE2 (p = 0.021 and p < 0.001, respectively), and COX-2 mRNA (p = 0.021 and p = 0.006, respectively). The IL-6 concentration was moreover significantly lower in the LPS-V(1000) group than in the LPS group (p < 0.001), whereas the IL-6 concentration in the LPS-V(100) and the LPS groups was not significantly different.

Conclusion

In a dose-dependent manner, vasopressin inhibited the endotoxin-induced upregulation of inflammatory mediators in activated murine macrophages.

Keywords
Chemokine; Cytokine; Lipopolysaccharide; Nitric oxide; Prostaglandin E2