Natural killer cell activity and sensitivity to positive and negative modulation in uncomplicated obese subjects: relationships to leptin and diet composition

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Abstract

BACKGROUND:

Natural killer (NK) cells are a key component of innate immunity; their activity is modulated by cytokines and hormones and is influenced by diet. In obesity, a higher risk of cancer and infections has been demonstrated. Studies on NK cell activity have yielded inconsistent results; NK cell sensitivity to modulators has not been assessed before.

OBJECTIVE:

In this case-control study, we assessed both spontaneous NK cell activity and responsiveness to positive (interleukin (IL)-2) and negative (cortisol) modulators in uncomplicated obesity; we searched for correlations between NK cell activity and anthropometric, dietary and metabolic variables.

METHODS:

In all, 21 obese (six males/15 females) and 21 age- and sex-matched healthy nonobese subjects underwent clinical examination and dietary and laboratory analyses. Spontaneous and modulated NK activities of peripheral blood mononuclear cells were measured by enzyme-release cytotoxicity assay.

RESULTS:

Spontaneous NK cell activity was not different in obese subjects vs controls. IL-2 stimulated and cortisol inhibited NK cell activity in both populations. Cortisol-dependent inhibition was lower in the obese than in the control group (−24.4±2.9 vs −38.6±3.3%, P=0.002), but decreased sensitivity was restricted to women (P=0.0007). In obese subjects, cortisol-dependent inhibition negatively correlated with serum leptin levels (r=−0.54, P=0.02) and, in women, with body mass index (r=−0.63, P=0.01); IL-2-dependent stimulation positively correlated with dietary carbohydrates (r=0.61, P=0.005) and serum LDL levels (r=0.55, P=0.009) and negatively correlated with dietary lipids (r=−0.71, P=0.0006).

CONCLUSION:

Spontaneous and IL-2-inducible NK cell activity is normal in uncomplicated obesity. Sensitivity to IL-2 correlates with fat and carbohydrate intake. Sensitivity to glucocorticoids negatively correlates with serum leptin levels and is significantly diminished in obese women, in whom it correlates with body mass index.

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