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.
Ho
A D
AD
Department of Internal Medicine and Poliklinik, University of Heidelberg, F.R.G.
Männel
D N
DN
Wulf
G
G
Kirchner
H
H
Gundt
A
A
Trede
I
I
Rensch
K
K
Hunstein
W
W
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