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Tuesday 01 July 2003

Dobutamine modulates lipopolysaccharide-induced macrophage inflammatory protein-1alpha and interleukin-8 production in human monocytes.

By: Li CY, Tsai CS, Hsu PC, Wu CT, Wong CS, Ho ST.

Anesth Analg 2003 Jul;97(1):210-5, table of contents

Chemokines mediate the migration of leukocytes to sites of inflammation. The CC chemokine macrophage inflammatory protein (MIP)-1alpha and the CXC chemokine interleukin (IL)-8 are reported to play an important role in early inflammatory stages, wound healing, sepsis, and some cardiovascular diseases, including acute coronary syndromes and congestive heart failure. We conducted this study to investigate the effect of dobutamine on lipopolysaccharide (LPS)-induced MIP-1alpha and IL-8 production by human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 or 16 h at 37 degrees C in the presence or absence of dobutamine. The effect of dobutamine on MIP-1alpha and IL-8 synthesis was examined by using an enzyme-linked immunosorbent assay, and MIP-1alpha and IL-8 messenger RNA (mRNA) were examined by using reverse transcriptase-polymerase chain reaction. Dobutamine significantly inhibited LPS-induced MIP-1alpha and IL-8 production by THP-1 cells in a dose-dependent manner. Salbutamol had a similar suppressive effect on LPS-stimulated MIP-1alpha and IL-8 production. MIP-1alpha mRNA was also suppressed by 10 micro M dobutamine, whereas, at the same concentration, dobutamine had no significant effect on the IL-8 mRNA level. Moreover, we found that dobutamine suppressed the MIP-1alpha-induced chemotaxis in THP-1 differentiated macrophages. These findings suggest that dobutamine may inhibit macrophage chemotaxis, as well as MIP-1alpha and IL-8 production by monocytes. The site of chemokine regulation is at the transcriptional level for MIP-1alpha and might be at the posttranscriptional level for IL-8. IMPLICATIONS: Macrophage inflammatory protein (MIP)-1alpha and interleukin (IL)-8 are reported to play an important role in early inflammatory stages, wound healing, sepsis, and some cardiovascular diseases. Our study suggests that dobutamine may inhibit macrophage chemotaxis, as well as lipopolysaccharide-induced MIP-1alpha and IL-8 production by human monocytes.

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