Stimulation of Interleukin-1 ß Production may be Involved in Unresponsiveness to Erythropoietin Therapy

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1ß, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 ß production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 ß during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 ß, and there was a significant difference between the two groups. Induction of IL-1 ß by rHuEPO may be one cause of persistent anemia in dialysis patients.

Download Full-text

Investigation of the Influenza-Like Symptoms Associated with Recombinant Human Erythropoietin Therapy

Journal of International Medical Research ◽

10.1177/030006059702500302 ◽

1997 ◽

Vol 25 (3) ◽

pp. 127-134 ◽

Cited By ~ 6

Author(s):

A Takemasa ◽

N Yorioka ◽

M Yamakido

Keyword(s):

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Recombinant Human Erythropoietin ◽

Mononuclear Cells ◽

Interleukin 1 ◽

Tumour Necrosis Factor Α ◽

Peripheral Blood Mononuclear ◽

Human Erythropoietin ◽

Factor Α ◽

Necrosis Factor

The mechanism by which fever and influenza-like symptoms occur, after the administration of recombinant human erythropoietin (rHuEPO) to patients on continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood mononuclear cells, obtained from two patients with fever and/or influenza-like symptoms related to the administration of rHuEPO for the treatment of anaemia were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of interleukin-1 β and tumour necrosis factor-α was higher in cultures with rHuEPO than in cultures without rHuEPO, although the dose relationships were not clear. These findings suggest that increased production of interleukin-1 β and tumour necrosis factor-α, induced by administration of rHuEPO, may cause fever and influenza-like smptoms.

Download Full-text

Recombinant Human Erythropoietin Increases lnterleukin-1β Production in Cultured Peripheral Blood Mononuclear Cells from Patients Resistant to Recombinant Human Erythropoietin Therapy

Nephron ◽

10.1159/000187968 ◽

1994 ◽

Vol 67 (2) ◽

pp. 245-247 ◽

Cited By ~ 5

Author(s):

Atsuo Takemasa ◽

Noriaki Yorioka ◽

Takafumi Ito ◽

Kazuomi Yamashita ◽

Hiroaki Oda ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Recombinant Human Erythropoietin ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Human Erythropoietin ◽

Blood Mononuclear Cells

Download Full-text

Stimulation of production of prostaglandin E in gingival cells exposed to products of human blood mononuclear cells

Biochemical Journal ◽

10.1042/bj1980391 ◽

1981 ◽

Vol 198 (2) ◽

pp. 391-396 ◽

Cited By ~ 16

Author(s):

S M D'Souza ◽

D J Englis ◽

A Clark ◽

R G Russell

Keyword(s):

Mononuclear Cell ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Gingival Tissue ◽

Prostaglandin E ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Gingival Cells ◽

Stimulation Of

1. Supernatant media from cultures of unstimulated human peripheral blood mononuclear cells contained one or more factors that increased by several hundred-fold the production of prostaglandin E by fibroblast-like cells derived from both inflamed and normal human gingival tissue. 2. This stimulation occurred in a dose-dependent manner and was completely inhibited by 14 microM-indomethacin. 3. Responsiveness to the factor declined as the age of the cell culture increased. 4. An increase in prostaglandin E production was first observed after a 2h exposure to the mononuclear cell factor(s) and could be prevented by cycloheximide. 5. Brief exposure (0.5 and 1.0 h) to mononuclear cell factor did not increase prostaglandin E production by the cells in a subsequent 72 h incubation in the absence of mononuclear cell factor. 6. Addition of arachidonate (10 microM and 15 microM) further enhanced stimulation of prostaglandin E production in response to mononuclear cell factor. 7. The stimulatory activity was resistant to digestion by trypsin, but was heat-labile, so that only 17% remained after treatment at 56 degrees C for 30 min.

Download Full-text