Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin

P. P. Trotta, A. Tedde, S. Ikehara, Rajendra Pahwa, R. A. Good, M. E. Balis

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The effect of continuous infusion into C57BL/6J mice of 2'-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCl infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting a lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lymphocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coli lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.

Original languageEnglish (US)
Pages (from-to)2189-2196
Number of pages8
JournalCancer Research
Volume41
Issue number6
StatePublished - 1981
Externally publishedYes

Fingerprint

Pentostatin
Immunosuppressive Agents
Spleen
Stem Cells
Adenosine Deaminase Inhibitors
Bone Marrow Cells
Inbred C57BL Mouse
Mitogens
Thymus Gland
Lymph Nodes
Bone Marrow
T-Lymphocytes
Adenosine Deaminase
Phytohemagglutinins
Graft vs Host Disease
Lymphocyte Activation
Concanavalin A
Hepatitis
Lipopolysaccharides
Weight Loss

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Trotta, P. P., Tedde, A., Ikehara, S., Pahwa, R., Good, R. A., & Balis, M. E. (1981). Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin. Cancer Research, 41(6), 2189-2196.

Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin. / Trotta, P. P.; Tedde, A.; Ikehara, S.; Pahwa, Rajendra; Good, R. A.; Balis, M. E.

In: Cancer Research, Vol. 41, No. 6, 1981, p. 2189-2196.

Research output: Contribution to journalArticle

Trotta, PP, Tedde, A, Ikehara, S, Pahwa, R, Good, RA & Balis, ME 1981, 'Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin', Cancer Research, vol. 41, no. 6, pp. 2189-2196.
Trotta PP, Tedde A, Ikehara S, Pahwa R, Good RA, Balis ME. Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin. Cancer Research. 1981;41(6):2189-2196.
Trotta, P. P. ; Tedde, A. ; Ikehara, S. ; Pahwa, Rajendra ; Good, R. A. ; Balis, M. E. / Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin. In: Cancer Research. 1981 ; Vol. 41, No. 6. pp. 2189-2196.
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