**3. Conclusion**

188 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

p < 0.05

Patients Non-Outlier Range

Healthy PMA

Patients PMA

Healthy

p < 0.05

microglobulin was significantly reduced (unpublished data).

at the site of interstitial inflammation (unpublished data).

**2.2.4 Concentrations of chemokines** 

0

10

20

30

40

50

60

70

Patients fMLP

p < 0.05

Healthy fMLP

Fig. 6. Respiratory burst (MFI) in monocytes at the site of intense interstitial inflammation.

Patients on high-flux hemodialysis/hemodiafiltration had significantly higher concentrations of MCP-1, MIP-1α, IL-6, IL-8, TNF-α and high-sensitivity CRP (hsCRP) in the peripheral circulation, prior to dialysis treatment, compared with healthy subjects (Olsson et al. 2009). MMP-9/NGAL serum concentration was similar in patients on high-flux hemodialysis/hemodiafiltration and healthy subjects (Olsson et al. 2009). Significantly higher serum levels of β2-microglobulin and serum amyloid A (SAA) were observed in patients on high-flux hemodialysis/hemodiafiltration, compared with healthy subjects. The serum concentrations of chemokines, hsCRP, SAA and oxidized LDL were not influenced by the high-flux hemodialysis/hemodiafiltration session, while the concentration of β2-

The concentrations of MIP-1α, MMP-9/NGAL and IL-8 at the sites of intermediate and intense inflammation were similar in patients and healthy subjects, and the concentration of MCP-1 at the sites of intermediate and intense inflammation was significantly higher in patients on highflux hemodialysis/hemodiafiltration, compared with healthy subjects (Olsson et al. 2009). At the site of intermediate inflammation, the concentration of IL-6 and TNF-α was significantly higher in patients compared with healthy subjects, reflecting a high inflammatory activity (unpublished data). There were no significant correlations between the concentrations of chemokines or the gradient between the concentration in the peripheral circulation and the interstitium, and the recruitment of neutrophils and monocytes and their expression of CD11b

 Median 25%-75% *In vivo* extravasated monocytes and neutrophils from patients on high-flux hemodialysis/hemodiafiltration have a preserved capacity to mobilize CD11b, compared with the corresponding cells from healthy subjects (Olsson et al. 2007). Furthermore, monocytes and neutrophils were able to respond to a second signal (fMLP) at the site of interstitial inflammation, indicating an adequate response to bacterial peptides (Olsson et al. 2007). After the most potent stimulation, both monocytes and neutrophils that had extravasated *in vivo* and been recruited to the site of intense inflammation showed a lower capacity to produce hydrogen peroxide in response to activation, compared with the corresponding cells from healthy individuals (Olsson et al. 2007). The apoptotic rates of neutrophils and monocytes were similar in patients and in healthy subjects (Olsson et al. 2007). Clearance of leukocytes from the site of infection via apoptosis is essential for the coordinated resolution of inflammation. The balance between pro-apoptotic and antiapoptotic factors is necessary for the maintenance of an effective immune response without the harmful side effects of an excessive neutrophil activation.

The higher concentration of MCP-1 and equal concentration of IL-8, MMP-9/NGAL and MIP-1α at the sites of intermediate and intense inflammation in patients on high-flux hemodialysis/hemodiafiltration (Olsson et al. 2009) could be of importance for the maintained capacity of leukocytes to extravasate and mobilize CD11b compared with healthy subjects (Olsson et al. 2007). These data contrast with our previous studies on patients with chronic kidney disease or patients on peritoneal dialysis, in which the concentrations of MCP-1 and IL-8 are significantly lower, coupled with an impaired capacity to up-regulate CD11b on neutrophils at sites of interstitial inflammation (Dadfar et al. 2004c; Dadfar et al. 2004b, 2004a).

The results of our study support a preserved neutrophil and monocyte function in terms of extravasation and activation at the inflammatory focus. One possible explanation for the preserved capacity of monocytes and neutrophils to express CD11b in response to an interstitial inflammation in patients on high-flux hemodialysis/hemodiafiltration may be that the cells extravasate into a milieu which contains equal or higher concentrations of factors involved in transmigration and CD11b expression (MCP-1, IL-8, MIP-1α and MMP-9/NGAL) compared with healthy subjects. The maintained capacity to produce chemokines in the interstitium in patients on high-flux hemodialysis/hemodiafiltration may be due to an increased intradialytic removal of uremic substances that inhibit leukocyte function.
