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).


CONCLUSIONS
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.
Dovio
A
A
Internal Medicine Unit, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy. dovioaa@libero.it
Caramello
V
V
Masera
R G
RG
Sartori
M L
ML
Saba
L
L
Tinivella
M
M
Prolo
P
P
Termine
A
A
Avagnina
P
P
Angeli
A
A
D000328:Adult; D000886:Anthropometry; D015992:Body Mass Index; D016022:Case-Control Studies; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000276:immunology*
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007376:Interleukin-2; D020738:Leptin; D006854:Hydrocortisone