[Pattern of blood levels of erythropoietin and proinflammatory cytokines in patients with anemia of chronic disorders secondary to infection]. / Perfil de los niveles séricos de eritropoyetina y citocinas proinflamatorias en pacientes con anemia de trastornos crónicos secundaria a infección.

OBJECTIVE: To evaluate the pattern of erythropoietin (EPO) and some proinflammatory cytokines in the anemia of chronic disorders (ACD) secondary to infection. METHODS: Sequential determination in serum of interleukin-1 beta (IL-1 beta), necrosis tumoral factor alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-6 (IL-6), and erythropoietin (EPO) in 25 patients with chronic bacterial infectious diseases and ACD criteria. We evaluated the relationship of these mediators with the anemia and the iron metabolism. RESULTS: Serum EPO levels significatively decreased compared with initial values, and the last control was in normal rank (18.04 +/- 19.10 vs. 8.56 +/- 4.72 UI/mL; p < 0.001; normal rank: 4-15 mUI/mL). In the first control, there was a negative and non significative correlation between the EPO levels and the hemoglobin concentration (r = -0.115, NS), reaching significance in the last control (r = -0.446; p < 0.05). There was negative correlation between the hematocrit and TNF-alpha levels (r = 0.467; p < 0.05) and between the haemoglobin values and the log of serum TNF-alpha (r = 0.424; p < 0.001). An inverse correlation between the IL-6 levels and both, the hemoglobin concentration and the serum iron was found, and there was a direct correlation between this cytokine values and the EPO levels. CONCLUSIONS: Blunted response of erythropoietin and the action of TNF may contribute to the pathogenesis of ACD secondary to infection. Positive correlation between IL-6 and EPO suggest a proerythropoietic action of IL-6 in response to the anemia.

Perfil de los niveles séricos de eritropoyetina y citocinas proinflamatorias en pacientes con anemia de trastornos crónicos secundaria a infección / Pattern of erythropoietin and proinflammatory cytokines in serum from patients with anemia of chronic disorders secondary to infection

Objetivo: Evaluar el comportamiento de la eritropoyetina (EPO) y determinadas citocinas proinflamatorias en la anemia de trastornos crónicos (ATC) de origen infeccioso. Métodos: Determinación secuencial en suero mediante enzimoinmunoanálisis de interleucina-1 beta (IL-1 ), factor de necrosis tumoral alfa (TNF- ), interferón gamma (IFN-), interleucina-6 (IL-6) y eritropoyetina (EPO) en 25 pacientes con enfermedades de origen bacteriano, curso clínico prolongado y criterios de ATC. Se analizó la relación de estos mediadores con la anemia y con el metabolismo del hierro. Resultados: Los niveles de EPO experimentaron un descenso significativo respecto al nivel inicial, normalizándose en el control tardío (18,04 ± 19,10 vs 8,56 ± 4,72 UI/mL; p < 0,001; rango normal: 4-15 mUI/mL). Inicialmente, existía correlación inversa no significativa entre los niveles de EPO y la concentración de hemoglobina (r = - 0,115, NS), alcanzándose significación estadística en el control tardío (r = -0,446; p < 0,05). Existía correlación inversa entre el hematocrito y los niveles del TNF- (r = 0,467; p < 0,05) y entre la hemoglobina y la transformación logarítmica del TNF (r = 0,424; p < 0,001). La IL-6 mostró correlación inversa con la hemoglobina (r = 0,366; p < 0,05) y con la sideremia (r = 0,614; p < 0,001), mientras que se correlacionó directamente con los niveles de la EPO (r = 0,297; p < 0,05). Conclusiones: Una deficiente respuesta de la eritropoyetina y la acción del TNF pueden implicarse en la patogenia de la ATC de origen infeccioso. La correlación positiva entre la IL-6 y la EPO sugiere una implicación proeritropoyética de la primera en respuesta a la anemia (AU)

Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity.

Anemia of CRF has been corrected by use of H-R-EPO both in hemodialysis and CAPD patients. Long term response to subcutaneous EPO and its relationship with serum EPO levels remain to be established. Twenty-five CAPD patients treated with CAPD during 30 +/- 28 (mean +/- SD) months were included in this study. The follow-up period was 6-24 months. All patients have been on CAPD at least 6 months and their Hemoglobin (Hb) level was lower than 8.5 g/dl. Twelve patients received EPO by subcutaneous route, at doses of 20 u./Kg daily and 13 other patients at doses of 2000 units twice a week. Thereafter, these doses were adjusted to obtain a Hemoglobin level ranging 10.5-13 g/dl. In conclusion, our results suggest that the subcutaneous route for H-R-Erythropoietin can be considered as the best choice for CAPD patients. Low doses twice a week seem to improve anemia in 2 months. Later, dose adjustment should be done according to the patient's response. The improvement in nutritional status we observed suggests a new positive aspect for EPO therapy. Our data did not show changes in peritoneal function.

Treatment of the anemia with human recombinant erythropoietin in CAPD patients.

Three homogenous groups of CAPD patients, all of them with plasma hemoglobin levels lower than 8 g/dl were studied. Group 1 included 8 patients who received EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2 included 7 patients treated with EPO by subcutaneous route but at doses of 2000 units twice a week. Group 3 was constituted by 4 patients receiving EPO by intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All patients showed an increase in hematocrit and Hb levels after three months of treatment, but the mean EPO dose was quite different comparing the groups, maintaining the reached levels at the 9th month; reticulocyte count increased only during the first month. The rest of clinical and biochemical parameters did not suffer any significant modifications. Our features showed a higher profit, that is, higher increase in Hb level with lower dose of EPO in the s.c. group in respect to i.p. group. Furthermore, we have registered a marked increase in the frequency of exogenous peritonitis in these particular patients while using i.p. EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an ideal way for this treatment, resulting in a more adequate profit ratio than that described in hemodialysis patients. The intraperitoneal route is more expensive and risky for the peritoneum, probably as a consequence of the increase of manipulations.

Hemolytic anemia and susceptibility to hydrogen-peroxide hemolysis in children with vitamin E-deficiency and chronic liver disease.

Thirty-four children, aged 1-14 years, with severe chronic liver disease were studied to determine the incidence of chronic hemolytic anemia and the mechanism underlying it. Sixteen children were grouped as vitamin E-deficient patients (Group I, serum vitamin E level below 5.0 micrograms/ml) and compared with 18 vitamin E-sufficient children (Group II) and 20 healthy controls. Group I patients had a significantly lower hemoglobin level (11.6 +/- 0.4 g/dl) when compared with Group II (12.9 +/- 0.4 g/dl, less than 0.05), their RBC's were less resistant to H2O2-induced hemolysis (53.1 +/- 8.0% in Group I, vs. 1.07 +/- 0.23% in Group II), and the average hemolysis correlated with serum vitamin E levels. H2O2-induced hemolysis reverted to normal in five patients after vitamin E therapy. With respect to controls, cirrhotic children in both groups showed a slight increase in total RBC membrane lipids, but no difference in either phospholipid content or in cholesterol/phospholipid molar ratio that could have changed RBC membrane properties and sensitivity to lysis. In our experience, vitamin E-deficient cirrhotics have a slight degree of chronic hemolytic anemia and their RBC's are much more sensitive to H2O2 lysis, although this abnormal lysis susceptibility does not seem apparently related to membrane peroxidation.