Abstract
BackgroundObese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independantly associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects.Methodology and Principal FindingsClinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m2) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/− 13% vs 42% +/−12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01).Conclusions/SignificanceObese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.
Highlights
Obesity and smoking, independently are important factors for ill health
Natural killer cells (NK) cell cytotoxic function, measured by their ability to kill K562 tumour cells in vitro, was significantly reduced in obese subjects compared to lean controls
Our findings show a marked reduction in the numbers and function of NK cells in obese individuals
Summary
Independently are important factors for ill health. A recent meta-analysis has shown that obesity is associated with 25–40% of certain malignancies [1], in particular oesophageal adenocarcinoma, thyroid, renal and colon cancers, multiple myeloma and leukaemia in both obese men and women. Obese individuals who smoke have a 14 year reduction in life expectancy at the age of 40 [4]. A large prospective study has shown that smoking coupled with obesity contributes substantially to all-cause mortality, with 3.5 to 5-fold risks for severely obese current smokers compared to normal weight non-smokers [5]. Obese smokers have an increased risk of developing both Type 2 Diabetes [6] and cancer [5]. How smoking and obesity might interact to reduce life expectancy is not clear. Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independantly associated with increased risk of malignancy. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects
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