Uremia is associated with impairment of various cell-mediated immunity functions. The effect of parathyroid hormone (PTH) – known to be elevated in uremia – on several T cell functions has been studied. Normal peripheral blood lymphocytes incubated with increasing amounts of human PTH (HPTH) or bovine PTH (BPTH) showed a considerable decrease (up to 40%) in lectin-induced lymphocytes transformation, significant decrease in helpers to suppressors ratio, and marked inhibition of E rosette formation and T_ιrpositive cells. PTH alone showed no cytotoxic effect on lymphocytes when incubated with or without mitogens. Glucagon, in concentrations up to 10-fold those found on uremia, had no effect on T cell function. Thus the effect of PTH was specific to the hormone action. The direct effect of PTH on normal T lymphocytes and some of their immunological responses is not clear. However, the results of this study support the hypothesis that excess blood levels of PTH may play a role in the pathogenesis of the impairment of the immune response in uremia.

In the present study, activity of polymorphonuclear leukocyte (PMNL) intra-cellular antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), was assessed in CRF patients on hemodialysis (HD), or continuous ambulatory peritoneal dialysis (CAPD) and in healthy controls. The activity of SOD and GPX was reduced in HD and in CAPD (SOD: by 34.2 and 42%, respectively, and GPX 66 vs. 42%, respectively, taking the activity in normal controls as 100%). Catalase activity, on the other hand, was significantly augmented (298 and 175%, respectively) as compared to the healthy controls. This impairment in antioxidant enzymes activity, involved in the respiratory burst and phagocytosis, may contribute to the understanding of the reduced bactericidal ability of PMNL activity found in these patients.

Uremic patients undergoing hemodialysis (HD) are known to be highly susceptible to infections. Recent data indicate that in addition to its well-known stimulating effects on red cell production, erythropoietin (EPO) may also have immunomodulating properties. The aim of this study was to examine the effect of EPO on lectin-induced T-lymphocyte transformation in uremic patients, as part of its effect on the immune response. Sixteen HD patients and 20 age- and sex-matched healthy controls were compared before and after 6 and 20 weeks of EPO treatment. T lymphocytes were analyzed for their mitogenic activity following treatment with phytohemagglutinin (PHA), concanavalin A (CON A) and anti-CD3 by measuring ³H-thymidine incorporation. HD patients showed reduced mitogenic responses to all mitogens tested, compared to healthy controls. During the 6 weeks of EPO administration, a significant increase in T-lymphocyte activity could be demonstrated following exposure to all three mitogens (PHA, from 32 ± 2 to 45 ± 8; CON A, from 11 ± 3 to 25 ± 9; anti-CD3, from 11 ± 3 to 22 ± 5, means ± SD). This increase was augmented after 5 months of EPO treatment. We conclude therefore that EPO improves in vitro T-cell mitogenic proliferation, even after short periods of treatment.

The notion that parathyroid hormone (PTH) can serve as an immunomodulator was examined. T cell function tests were performed in 3 patients with primary hyperparathyroidism before and 1 month after parathyroidectomy (PTX). Three normal volunteers, age and sex matched, were used as controls. One patient with lipoma of the neck was also examined before and after surgical removal of the lesion. In the primary hyperparathyroidism patients the total T cells were lower, the suppressors were higher and the helper to suppressor ratio was significantly lower than in control subjects. The lectin-stimulated lymphocyte transformation was significantly inhibited. All these abnormalities were restored to normal after PTX. Depressed lymphocyte activity was found also in the patient with lipoma. However, no change occurred after surgery. These results support the assumption that excess blood levels of PTH may have an immunosuppressive effect.

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O₂. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O₂ resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia. However, glomerular filtration rate (GFR) and fractional excretion of sodium (FE_Na) did not correlate to the enzyme activities. Thus, no increase in GFR or decrease in FE_Na were seen after 90 min of reperfusion despite increase in enzyme activities above postischemic values. Moreover, these functions were not aggravated by hyperoxia as was expected. On the contrary, GFR rose slightly and FE_Na decreased significantly after 90 min of reflow under 100% O₂. These results may indicate that if ROS are involved in the development of postischemic damage, a different mechanism -induced by hyperoxia – may exist which protects the kidney from massive injury. Some possible mechanisms are discussed.