Effect of surgically-induced weight loss on leukocyte indicators of chronic inflammation in morbid obesity

Abstract

Background: Recent evidence suggests that morbid obesity is a chronic inflammatory condition that may be associated with immune dysfunction. To test this hypothesis, we investigated several leukocyte cell surface markers of chronic inflammation and followed their response to surgically-induced weight loss.

Methods: 26 patients having Roux-en-Y gastric bypass (RYGBP) for morbid obesity (BMI > 40) were compared to 10 normal controls (BMI < 25). Relative monocyte and neutrophil frequencies and expression of the activation antigens CD11b (adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry preoperatively and at 1, 3, 6 and 12 months after RYGBP. Cases served as their own controls but were also compared to non-obese controls. The results were statistically analyzed using Student's t-test and ANOVA for parametric values and Mann-Whitney along with Kruskal-Wallis ANOVA for nonparametric values.

Results: The control group had mean age 37 +/- 7.6 with mean 23 +/- 2.5 and no comorbidities. The mean age of the sample group was 40.36 +/- 13.7 with mean BMI 52 +/- 8.2. The neutrophil and monocyte relative frequencies of CD11b (monocytes and neutrophils), and CD16 (neutrophils only) were comparable to controls at baseline and did not change significantly with weight loss throughout the study period. However, a significant reduction of CD62L (L-selectin) expression was noted in monocytes and neutrophils at baseline (neutrophils 103 vs 240 gmf, p < 0.001) (monocytes 104 vs 246 gmf, P < 0.001) when compared to normal controls. Levels of L-selectin normalized by 6 months in both monocytes and neutrophils, and by 12 months had become abnormally elevated in monocytes (monocytes 391 gmf, P = 0.007); in neutrophils, there was an upward trend that did not reach significance. The expression of the LPS receptor CD14 in the study group was elevated significantly compared to controls at baseline (1129 vs 719 gmf, P = 0.004); this marker appeared to return to normal by 3 months. Monocyte CD14+/CD16+ subset percentage were also elevated significantly at baseline (14.3% vs 5.25%, P < 0.001), declined throughout the time period but was still significant at 1 year (8.8%, P < 0.001). Eosinophil percentages were elevated at baseline (3.3% obese vs 1.8% controls, P = 0.003) and remained so throughout the time period.

Conclusion: Deficiencies in the immune system of morbidly obese individuals include elevated levels of eosinophils, monocyte CD14, and monocyte CD14+/CD16+ subsets, with depression of monocyte and neutrophil CD62L. These abnormal levels reverse rapidly with surgically-induced weight loss. RYGBP is not only a weight loss operation but also appears to be an immune restorative procedure.