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CRITICAL CARE AND TRAUMA

Dobutamine Modulates Lipopolysaccharide-Induced Macrophage Inflammatory Protein-1 and Interleukin-8 Production in Human Monocytes

Chi-Yuan Li, MD MS^*, Chien-Sung Tsai, MD, Ping-Ching Hsu, MS, Ching-Tang Wu, MD^*, Chih-Shung Wong, MD PhD^*, and Shung-Tai Ho, MD MS^*

Departments of *Anesthesiology and Surgery, Tri-Service General Hospital, National Defense Medical Center, National Defense University, Taipei, Taiwan, Republic of China

Address correspondence and reprint requests to Chi-Yuan Li, MD, MS, Department of Anesthesiology, #325, Section 2, Cheng-Kung Rd., Taipei, Taiwan, ROC. Address e-mail to cyli{at}ndmctsgh.edu.tw

Chemokines mediate the migration of leukocytes to sites of inflammation. The CC chemokine macrophage inflammatory protein (MIP)-1 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-1 and IL-8 production by human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 4 or 16 h at 37°C in the presence or absence of dobutamine. The effect of dobutamine on MIP-1 and IL-8 synthesis was examined by using an enzyme-linked immunosorbent assay, and MIP-1 and IL-8 messenger RNA (mRNA) were examined by using reverse transcriptase-polymerase chain reaction. Dobutamine significantly inhibited LPS-induced MIP-1 and IL-8 production by THP-1 cells in a dose-dependent manner. Salbutamol had a similar suppressive effect on LPS-stimulated MIP-1 and IL-8 production. MIP-1 mRNA was also suppressed by 10 µM 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-1-induced chemotaxis in THP-1 differentiated macrophages. These findings suggest that dobutamine may inhibit macrophage chemotaxis, as well as MIP-1 and IL-8 production by monocytes. The site of chemokine regulation is at the transcriptional level for MIP-1 and might be at the posttranscriptional level for IL-8.

IMPLICATIONS: Macrophage inflammatory protein (MIP)-1 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-1 and IL-8 production by human monocytes.

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