Selective sequestration of cytokine-producing monocytes during hemodialysis treatment.

Hemodialysis treatment leads to leukocyte activation and cytokine production. Studying this effect has been complicated because cell activation by blood membrane contact also induces adherence factors on leukocytes, leading to margination of cells to the endothelium of the lung. Using single-cell cytokine determination, we studied the relation between cytokine production and cell sequestration during dialysis therapy. Blood was sampled in 11 chronic hemodialysis patients using hemophane dialyzers before hemodialysis and at 20 and 120 minutes of treatment. Lipopolysaccharide (LPS)-induced cytokine production in monocytes was studied by intracellular staining for interleukin-6 (IL-6) and IL-10 and flow cytometry. Results obtained in dialysis patients were compared with samples from an ex vivo dialysis system. Monocyte maturation stage was evaluated by detection of several surface markers through flow cytometry. Within 20 minutes of hemodialysis, the numbers of circulating monocytes decreased to one third of initial values. Before dialysis, 56.7% +/- 15.7% of circulating monocytes responded to LPS by the production of IL-6. This fraction decreased to 21.1% +/- 17.3% (P < 0.001 versus before hemodialysis) at 20 minutes and 32.3% +/- 13.8% (P < 0.001 versus before hemodialysis) at 120 minutes of treatment. A similar decrease occurred for IL-10. Cytokine-positive cells did not decrease during ex vivo dialysis. Surface marker studies showed that mature monocytes expressing HLA-DR or CD86 were predominantly removed. We provide the first evidence for a subtype-specific sequestration of monocytes caused by dialysis treatment. Fully differentiated cells capable of cytokine production and antigen presentation are removed and relatively immature cells remain in circulation.

Lung volume reduction surgery versus conservative treatment in severe emphysema.

Lung volume reduction surgery (LVRS) has been proposed for patients with severe emphysema to improve dyspnoea and pulmonary function. It is unknown, however, whether prognosis and pulmonary function in these patients can be improved compared to conservative treatment. The effect of LVRS and conservative therapy were compared prospectively in 57 patients with emphysema, who fulfilled the standard criteria for LVRS. The patients were divided into two groups according to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM 58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/-1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no significant differences in lung function between the two groups at baseline; however, there was a tendency towards better functional status in the control group. The control group had a better modified Medical Research Council (MMRC) dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were used to estimate the differences between the two groups over 18 months. Significant improvements were observed in the LVRS group compared to the control group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea score and 6-min walking distance on all follow up visits. The estimated difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC 12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55; p<0.0001). In conclusion, lung volume reduction surgery is more effective than conservative treatment for the improvement of dyspnoea, lung function and exercise capacity in selected patients with severe emphysema.