[Show abstract][Hide abstract] 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.
Scandinavian journal of clinical and laboratory investigation 10/2012; · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with vitamin A/retinol deficiency are shown to be prone to infections and to suffer from increased inflammation, effects which can be remedied by vitamin A supplements. We aimed to study how human monocytes from the peripheral venous blood of healthy donors acted within the initial hours after adherence and exposure to bacterial endotoxin in the presence or absence of the 9-cis-isomer of retinoic acid (9cisRA). We found that adherent human monocytes were dominated by the CD14dimCD16+ subtype. Pretreatment with 9cisRA for 1 h significantly decreased lipopolysaccharide (LPS)-induced mRNA expression and protein release of tumor necrosis factor (TNF)α, interleukin (IL)-6 and chemokine ligands (CCL)3 and CCL4. In contrast, treatment with 9cisRA rapidly enhanced the production of monocyte chemoattractive protein/CCL2. 9cisRA treatment also led to enhanced migration of classical CD14high monocytes in a transwell in vitro system. We conclude that 9cisRA treatment of human adherent monocytes attenuates the inflammatory responses to LPS and induces the attraction of classical monocytes, a feature which may help explain why supplements administered to vitamin A-deficient patients counteract inflammation and increases the ability to fight infections.
Journal of Innate Immunity 12/2011; 4(2):176-86. · 4.46 Impact Factor