Human monocyte responses to lipopolysaccharide and 9-cis retinoic acid after laparoscopic surgery for colon cancer

Abstract

Surgery, even modern minimal invasive laparoscopic surgery, induces an initial inflammatory and acute phase response which is followed by a period of immunosuppression rendering surgical patients more susceptible to infection. Here, we aimed to study changes in monocyte inflammatory responses and inflammatory modulation mechanisms following laparoscopic colorectal surgery for colon cancer. Blood samples were collected from 19 colon cancer patients before, directly after and daily for 3 days following surgery. Blood cells were exposed ex vivo to bacterial lipopolysaccharide (LPS) or the inflammatory modulator 9-cis retinoic acid (9cisRA). In blood samples taken prior to surgery, we found significant pro-inflammatory responses to LPS, indicating classical monocyte activation. Directly after surgery, LPS induced significantly less early pro-inflammatory cytokines and monocyte/granulocyte-attracting chemokines. The LPS-mediated release of interleukin (IL)-1β was still significantly attenuated 3 days after surgery. In patient monocytes collected after surgery, we found increased levels of suppressors of cytokine signaling (SOCS)1 and SOCS3 mRNA, reported to be associated with polarization towards resolving macrophages. The retinoic acid isomer 9cisRA, reported to attenuate LPS-mediated inflammatory responses and alter chemokine responses in cultured monocytes, had a similar effect in patient blood. Three days after surgery, 9cisRA still attenuated pro-inflammatory responses, but the induction of monocyte chemoattractive protein (MCP)-1/CCL2 mRNA in monocytes was reduced. This study indicates changes in monocyte responses that last for at least 3 days after laparoscopic surgery.

Key Words::

• Cytokines
• chemokines
• monocytes
• gastrointestinal cancer surgery
• suppressor of cytokine signaling

Acknowledgements

We thank Aina M. Lian at the Oral research Laboratory, Institute for Clinical Dentistry, for performing multiplex analysis, and the clinical laboratory at Oslo University Hospital for CRP analysis and white blood cell counts.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Sources of financial support were the University of Oslo, Oslo University Hospital Rikshospitalet HF and Ullevaal HF, and the Norwegian Research Council.