|Tussing Humphreys, Lisa|
Submitted to: Cytokine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2010
Publication Date: 2/1/2011
Citation: Tussing Humphreys, L.M., Pini, M., Ponemone, V., Braunschweig, C., Fantuzzi, G. 2011. Suppressed cytokine production in whole blood cultures is related to iron status and is partially corrected following weight reduction in morbidly obese pre-menopausal women. Cytokine. 53:201-206. Interpretive Summary: Obesity is associated with increased adipose production of inflammatory molecules, systemic inflammation, and possibly defective immune response to infection. Impaired inflammatory molecule production by specific blood cells may cause this dysfunction. The primary aim of this study was to assess differences in the production of inflammatory molecules from the blood of obese and non-obese women, and change six-months following weight loss surgery in the obese group. Secondly, we explored relationships between iron status, a molecule that controls iron status, body mass index, waist circumference, and blood inflammatory molecule production in the obese and non-obese women. Results demonstrated that morbid obesity was associated with altered blood inflammatory molecule production compared to non-obese women. Also, iron status may be related to the production of specific inflammatory molecules in the blood. With weight loss, production of blood inflammatory molecules in the obese women was more similar to that observed in the non-obese women. Our findings justify the need for further studies aimed at investigating the mechanisms linking obesity, iron status and inflammatory molecule production as well as the potential clinical implications of these findings in terms of susceptibility to infection and autoimmune diseases as well as response to vaccination.
Technical Abstract: Assess ex vivo whole-blood cytokine production and its association with iron status in obese versus non-obese women. Determine the change in ex vivo whole-blood cytokine production six months after restrictive bariatric surgery in the obese group. Subjects were 17 obese (BMI: 46.6 ±7.9 kg/m2) and 19 non-obese (BMI: 22.5 ± 3.0 kg/m2), pre-menopausal women; frequency matched for hemoglobin, age, and race. Measurements were at baseline control and ex vivo stimulated IL-6, IL-10, IL-22, IFN', and TNFa from heparinized whole blood cultures, hemoglobin from finger-stick and transferrin receptor, hepcidin, hs-CRP, IL-6, HOMA-IR from fasted serum samples and anthropometric parameters were assessed in the women. All parameters were reassessed six-months following restrictive bariatric surgery in the obese women. The results were whole blood ex vivo production of IL-6, TNFa and IFN' was significantly reduced, IL-22 increased, and IL-10 was unaffected in obese compared with the non-obese women. Furthermore, ex vivo production of IL-6 and TNFa normalized, but IFN' production remained unchanged with weight loss following restrictive gastric surgery. In the obese women, serum transferrin receptor (a marker of iron status) and serum hepcidin were highly correlated with ex vivo IFN' production at baseline. Morbid obesity, in pre-menopausal women, is associated with altered cytokine production from peripheral blood leukocytes. In the obese state, iron status may be an important regulator of cytokine production, particularly for IFN'.