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J Thorac Cardiovasc Surg 1995;109:809
© 1995 Mosby, Inc.

BRIEF COMMUNICATIONS

Effect of recombinant erythropoietin on peripheral T lymphocytes

Kouichi Hisatomi, MDa, Masanobu Nakao, MDb, Tadashi Isomura, MDa, Kenichi Kosuga, MDa, Kyogo Itoh, MDb


Fukuoka, Japan

Recombinant erythropoietin Go 1 has commonly been used to reduce the volume of homologous blood transfusion in patients undergoing cardiac operations in Japan. We Go 2 have reported that recombinant erythropoietin treatment not only increased levels of circulating erythrocytes but also improved indices of cell-mediated immunity, and we Go 3 have suggested that it might help to ameliorate or prevent the impairment of immune function that can occur after cardiac operations. We subsequently administered recombinant erythropoietin in a dosage of 200 U/kg per day for 7 days in a patient with postoperative erythroderma associated with pancytopenia after a cardiac operation. The level of interleukin-2 production was also found to increase in association with lessening of symptoms. In the present study, we investigated the effect of recombinant erythropoietin on peripheral T cell response with the use of a reverse-transcriptase polymerase chain reaction (PCR), which has currently been acknowledged to detect cytokines in vitro in immunologic studies. Peripheral blood mononuclear cells were obtained 7 days postoperatively from 10 patients who underwent valvular operations. Five of the patients without complications were given recombinant erythropoietin in a dosage of 100 U/kg for 7 days, and the other five patients were not. Samples were prepared by the Ficoll-Conray method. They were adjusted to a concentration of 4 x 10 6 cells per milliliter and were incubated with 5, 10, 50, or 100 U/ml of recombinant erythropoietin for 6 hours at 37° C. Ribonucleic acid (RNA) was isolated by the RNAzol method (Biotecx Laboratories, Inc., Houston, Tex.). Cyclic deoxyribonucleic acid was prepared essentially as described by Becker, Quay, and Soukup. Go 4 The PCR primers used for this study were interleukin-2 primers (sense primer: 5'-TGTACAGGATGCAACTCCTGTCTT; antisense primer: 5'-GTTAGTGTTGAGATGATGCTTTGAC). PCR was performed for 35 cycles. Reverse-transcriptase PCR-amplified messenger RNA was electrophoresed in a 1.5% agarose gel and stained with ethidium bromide. Go 5 T cells separated from peripheral blood mononuclear cells mixed with 5 or 10 U/ml of recombinant erythropoietin did not express interleukin-2, whereas the samples mixed with 50 or 100 U/ml of recombinant erythropoietin had decreased expression regardless of whether patients received recombinant erythropoietin for 7 days after the operation. These findings suggest that, at the messenger RNA level, recombinant erythropoietin may inhibit production of interleukin-2 from T cells in proportion to the dose. These results suggest that further study will be needed to reveal the true effect of recombinant erythropoietin on cell-mediated immune responses.

Footnotes

From the Second Department of Surgerya and the Department of Immunology,b Kurume University School of Medicine, Fukuoka, Japan. Back

J THORAC CARDIOVASC SURG 1995;109:809 Back

References

  1. Jacobs K, Shoemaker C, Rudersdorf R, et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 1985;313:806-10.[Medline]
  2. Hisatomi K, Isomura T, Kawara T, et al. Changes in lymphocyte subsets, mitogen responsiveness, and interleukin-2 production after cardiac operations. J THORAC CARDIOVASC SURG 1989;98:580-91.[Abstract]
  3. Hisatomi K, Isomura T, Galli SJ, Yasunaga H, Hayashida N, Ohishi K. Augmentation of interleukin-2 production after cardiac operations in patients treated with erythropoietin. J THORAC CARDIOVASC SURG 1992;104:278-83.[Abstract]
  4. Becker S, Quay J, Soukup J. Cytokine (tumor necrosis factor, IL-6 and IL8) production by respiratory syncytial virus-infected human alveolar macrophages. J Immunol 1991;147:4307-12.[Abstract]
  5. Hoshino T, Yamada A, Honda J, et al. Tissue-specific distribution and age-dependent increase of human CD11b+T cells. J Immunol 1993;151:2237-46.[Abstract]




This Article
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Tadashi Isomura
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