Long-term effects of 2'-deoxycoformycin treatment on cytokine production in patients with hairy cell leukemia.
Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.
Department of Internal Medicine and Poliklinik, University of Heidelberg, F.R.G.
A D
AD
Ho
D N
DN
Männel
G
G
Wulf
H
H
Kirchner
A
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Gundt
I
I
Trede
K
K
Rensch
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W
Hunstein
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007372:Interferons / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000627:therapeutic use*; D012074:Remission Induction; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015649:Pentostatin; D007372:Interferons