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

International Journal of Obesity volume 28, pages 894–901 (2004)Cite this article

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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Acknowledgements

This work was supported by grants from the Ministero dell'Università e della Ricerca Scientifica, Cassa di Risparmio di Cuneo, Cassa di Risparmio di Saluzzo and Fondazione Rossini.

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Authors and Affiliations

  1. Department of Clinical and Biological Sciences, Internal Medicine Unit, University of Turin, Orbassano (TO), Italy

    A Dovio, V Caramello, R G Masera, M L Sartori, L Saba, A Termine & A Angeli

  2. Department of Clinical and Biological Sciences, Dietology Unit, University of Turin, Orbassano (TO), Italy

    M Tinivella & P Avagnina

  3. Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA, USA

    P Prolo

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Correspondence to A Dovio.

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Dovio, A., Caramello, V., Masera, R. et al. Natural killer cell activity and sensitivity to positive and negative modulation in uncomplicated obese subjects: relationships to leptin and diet composition. Int J Obes 28, 894–901 (2004). https://doi.org/10.1038/sj.ijo.0802639

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