Cytokine serum levels during treatment with high-dose recombinant human IL-3 in a patient with severe aplastic anemia.
A 37-year-old woman with severe aplastic anemia (SAA), who had relapsed 6 years after antilymphocyte globulin therapy, was treated with intravenous recombinant human IL-3 (4 micrograms/kg/d) for 21 days. Subsequently, long-term therapy with subcutaneous rhIL-3 at the highest dose level tested so far (16 micrograms/kg/d) was initiated in order to maintain growth-factor response. Therapy was discontinued on day 73 due to progressive thrombocytopenia and increased petechial bleeding. Both treatment schedules resulted in a transient increase in leukocytes (twofold) due to an increase in monocytes, neutrophils, and eosinophils. RhIL-3 had no effect on hemoglobin values or platelet counts and only marginally improved colony formation of bone marrow CFU-GM in response to rhGM-CSF. Side effects of both treatment schedules were mild and did not exceed WHO grade II. Steady-state serum concentrations of IL-3, which are able to stimulate hematopoiesis in vitro (i.e. > 1 ng/ml), were achieved by both low- and high-dose treatment, although high-dose treatment resulted in markedly higher serum levels of IL-3. On measuring cytokine serum levels (neopterin, IL-1 beta, IL-6, sIL-2R, GM-CSF, TNF-alpha, IFN-gamma) we noticed a different cytokine pattern with both treatment modalities, resulting in a moderate induction of TNF-alpha and IFN-gamma during low-dose, intravenous treatment, whereas during subcutaneous, high-dose treatment a profound increase of IL-6, sIL-2R, and, to a lesser extent, neopterin was detected. These results in a single patient with SAA indicate that further studies on IL-3 serum levels and IL-3-induced secondary cytokines in a larger group of patients are needed to optimize growth-factor treatment and to better understand the in vivo biological activity of IL-3.
Nachbaur
D
D
University Hospital, Department of Internal Medicine, Innsbruck, Austria.
Gratwohl
A
A
Herold
M
M
Tichelli
A
A
Slanicka
M
M
Nissen
C
C
Niederwieser
D
D
Speck
B
B
D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy*; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D016207:Cytokines / Q000097:blood*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007378:Interleukins / Q000378:metabolism; D007958:Leukocyte Count; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007377:Interleukin-3; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma