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

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.