Dysfunctional immune-privilege in morbid obesity: implications and effect of gastric bypass surgery.

BACKGROUND: Despite the epidemiological evidence linking obesity and cancer, there has never been a causal link. We believe the chronic inflammation present in obesity may predispose the obese to cancer through Fas-receptor over-expression and L-selectin under-expression in leukocytes, and elevated Fas ligand secretion in tumors affecting the morbidly obese. METHODS: Leukocytes from 25 patients having gastric bypass surgery were compared to 15 normal controls preoperatively and at 1, 3, 6, and 12 months postoperatively using flow cytometry to measure CD3, CD4, CD8, CD56, CD62 (L-selectin), CD69, and CD95 (Fas antigen) expression on T lymphocytes, B lymphocytes, natural killer cells, and neutrophils. RESULTS: The percentage of CD95 + T cells was significantly elevated from controls (69.4% vs 56%, P = 0.005). This difference persisted through 1 month postoperatively. Furthermore, expression of CD95 per cell, was significantly greater in these patients than that of the controls (80.2 vs 62.6 gmf, P = 0.018) preoperatively, and this continued to 1 month. Polymorphonuclear cells also displayed a similar elevation in CD95 gmf expression preoperatively (54.1 vs 40.7 gmf, P = 0.023) which normalized by 3 months. Natural killer cells did not display elevated numbers of CD95 gmf preoperatively, but they did experience a significant decline by 12 months. Additionally, there was significant reduction in the number of naiveT cells [(T cells without L-selectin (CD62L)], when compared to normals preoperatively (41.8% vs 51.3%, P = 0.001). There was no statistical difference between the postoperative patients and the controls by 3 months. CD69 was not different at baseline from controls in T or B cells, but there was a significant decrease by 12 months. CONCLUSION: The reduced expression of L-selectin combined with the elevated levels of CD95 suggests that morbid obesity predisposes patients to sites of immune privilege. This could be the mechanism for increased rates of cancer and wound infections seen in obesity. Surgically-induced weight loss eliminates these risk factors.

The effect of obesity on neutrophil Fc receptors and adhesion molecules (CD16, CD11b, CD62L).

BACKGROUND: There is a large body of epidemiological data associating obesity with a wide variety of clinical disease processes, including cancer and wound infections. However, defining the specific defects of neutrophils has proved difficult and often contradictory. METHODS: 27 patients having gastric bypass surgery for obesity (BMI > 40) were compared with 10 normal controls (BMI < 26). Relative neutrophil frequencies and expression of the activation antigens CD11b (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry. RESULTS: The study control group had a mean age of 37 +/- 7.6 yrs (range 30 to 57) with no significant health problems. Their mean BMI was 23 +/- 2.5 kg/m2 (range 21-26). The mean age of the sample group was 40.36 +/- 13.7 yrs (range 18 to 60) with a mean BMI of 52 +/- 8.2 kg/m2 (range 41 to 72). These patients had a large spectrum of diseases that afflict the morbidly obese, including hypertension (14), arthritis (10), exertional dyspnea (13), venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8 smokers. The neutrophil frequency in the obese patients was comparable to the controls (control 49% vs obese 51%). Additionally, there was no apparent difference between obese and controls regarding CD11b or CD16 expression (424 vs 498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L-selectin) expression noted in the morbidly obese with respect to controls (102 vs 303 gmf, p < 0.001). An increased percentage of eosinophils when compared to controls (6.7% vs 1.73%, p < 0.001) was also observed. CONCLUSION: Discordant CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil percentages support the hypothesis that a chronic inflammatory state exists in morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool possibly affect the neutrophil's ability to activate and migrate to sites of inflammation. This may play a role in the higher incidence of infectious complications seen in morbidly obese individuals.