Israel Medical Association Journal

Background: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs[1].

Objectives: To evaluate the effect of 20 weeks of EPO[2]-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.

Methods: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate.

Results: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC[3] and PMNL counts and ALP[4] activity following treatment. EPO retarded the deterioration in GFR[5]. The percent of PMNLs expressing EPO-R[6] was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.

Conclusions: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Objectives: To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia.

Methods: We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings.. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1.

Results: There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (± SD) leukocyte counts in the pediatric and adult groups were 21,018/mm (± 10,420) and 12,628/mm (± 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correslation was also found between age and platelet counts. Although cuytokine levels in both groups were not significantly different, age was

Conclusions: The immune response in community-aquired bronchopneumonia is, at least partly, age-dependent.

The leukocyte NADPH oxidase catalyzes the reduction of oxygen to O₂- (superoxide) at the expense of NADPH. The O₂- then dismutes to H₂O₂, which serves to oxidize Cl- to HOCl, a potent microbicidal agent that is used by leukocytes to kill invading microorganisms. This oxidation is catalyzed by myeloperoxidase. O₂ is also used to make other microbicidal oxidants, some in reactions with nitric oxide. The oxidase itself is highly complex, consisting of four unique subunits and Rac2. In the resting cell, two of the subunits, p22PHOX and gp91PHOX, are located in the membrane, and the other two, p47PHOX and p67PHOX, are in the cytosol. The electron-carrying components of the oxidase are

located in gp91PHOX; the NADPH binding site is generally regarded to be in gp91PHOX as well, but there is some evidence that it may be in p67PHOX. When the oxidase is activated, p47PHOX is phosphorylated at specific sites, and the cytosolic components plus Rac2 migrate to the membrane to assemble the active oxidase.