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Keywords
- CC16 (1)
- CLP (1)
- acute lung injury (1)
- bone metabolism (1)
- chest injury (1)
- cigarettes (1)
- complications (1)
- delayed wound healing (1)
- infection (1)
- macrophages (1)
- Smoking dependent alterations in bone formation and inflammation represent major risk factors for complications following total joint arthroplasty (2019)
- Numerous studies have described a correlation between smoking and reduced bone mass. This not only increases fracture risk but also impedes reconstruction/fixation of bone. An increased frequency of complications following surgery is common. Here, we investigate the effect of smoking on the clinical outcome following total joint arthroplasty (TJA). 817 patients receiving primary or revision (including clinical transfers) TJA at our level-one trauma center have been randomly interviewed twice (pre- and six months post-surgery). We found that 159 patients developed complications (infections, disturbed healing, revisions, thrombosis, and/or death). Considering nutritional status, alcohol and cigarette consumption as possible risk factors, OR was highest for smoking. Notably, mean age was significantly lower in smokers (59.2 ± 1.0a) than non-smokers (64.6 ± 0.8; p < 0.001). However, the number of comorbidities was comparable between both groups. Compared to non-smokers (17.8 ± 1.9%), the complication rate increases with increasing cigarette consumption (1–20 pack-years (PY): 19.2 ± 2.4% and >20 PY: 30.4 ± 3.6%; p = 0.002). Consequently, mean hospital stay was longer in heavy smokers (18.4 ± 1.0 day) than non-smokers (15.3 ± 0.5 day; p = 0.009) or moderate smokers (15.9 ± 0.6 day). In line with delayed healing, bone formation markers (BAP and CICP) were significantly lower in smokers than non-smokers 2 days following TJA. Although, smoking increased serum levels of MCP-1, OPG, sRANKL, and Osteopontin as well as bone resorption markers (TRAP5b and CTX-I) were unaffected. In line with an increased infection rate, smoking reduced 25OH vitamin D3 (immune-modulatory), IL-1β, IL-6, TNF-α, and IFN-γ serum levels. Our data clearly show that smoking not only affects bone formation after TJA but also suppresses the inflammatory response in these patients. Thus, it is feasible that therapies favoring bone formation and immune responses help improve the clinical outcome in smokers following TJA.
- Endogenous uteroglobin as intrinsic anti-inflammatory signal modulates monocyte and macrophage subsets distribution upon sepsis induced lung injury (2019)
- Sepsis is a serious clinical condition which can cause life-threatening organ dysfunction, and has limited therapeutic options. The paradigm of limiting excessive inflammation and promoting anti-inflammatory responses is a simplified concept. Yet, the absence of intrinsic anti-inflammatory signaling at the early stage of an infection can lead to an exaggerated activation of immune cells, including monocytes and macrophages. There is emerging evidence that endogenous molecules control those mechanisms. Here we aimed to identify and describe the dynamic changes in monocyte and macrophage subsets and lung damage in CL57BL/6N mice undergoing blunt chest trauma with subsequent cecal ligation and puncture. We showed that early an increase in systemic and activated Ly6C+CD11b+CD45+Ly6G− monocytes was paralleled by their increased emigration into lungs. The ratio of pro-inflammatory Ly6ChighCD11b+CD45+Ly6G− to patrolling Ly6ClowCD11b+CD45+Ly6G− monocytes significantly increased in blood, lungs and bronchoalveolar lavage fluid (BALF) suggesting an early transition to inflammatory phenotypes during early sepsis development. Similar to monocytes, the level of pro-inflammatory Ly6ChighCD45+F4/80+ macrophages increased in lungs and BALF, while tissue repairing Ly6ClowCD45+F4/80+ macrophages declined in BALF. Levels of inflammatory mediators TNF-α and MCP-1 in blood and RAGE in lungs and BALF were elevated, and besides their boosting of inflammation via the recruitment of cells, they may promote monocyte and macrophage polarization, respectively, toward the pro-inflammatory phenotype. Neutralization of uteroglobin increased pro-inflammatory cytokine levels, activation of inflammatory phenotypes and their recruitment to lungs; concurrent with increased pulmonary damage in septic mice. In in vitro experiments, the influence of uteroglobin on monocyte functions including migratory behavior, TGF-β1 expression, cytotoxicity and viability were proven. These results highlight an important role of endogenous uteroglobin as intrinsic anti-inflammatory signal upon sepsis-induced early lung injury, which modules the early monocyte/macrophages driven inflammation.
