In vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia.
Both IL-4 and IL-10 have been shown in vitro to inhibit leukemia cell secretion of IL-1beta, GM-CSF, and TNFalpha, and increase leukemia cell release of IL-1ra. In this study, we have investigated the in vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia (AML). Serum IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF levels were measured in AML patients who received IL-4, IL-10, or amifostine. No significant changes in the serum levels of IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF were found in AML patients who received amifostine. Both IL-4 and IL-10 were found to increase serum IL-1ra. This data is in accord with the in vitro studies. However, IL-4 increased serum GM-CSF levels and IL-10 increased serum IL-1beta and TNFalpha levels. These in vivo effects of the two cytokines differ from their in vitro effects. Despite the similar effects of IL-4 and IL-10 on cytokine production by AML cells in vitro, different effects were observed in AML patients in vivo. IL-4 increased serum SCF levels, whereas IL-10 decreased serum SCF levels. IL-4 increased serum GM-CSF levels, whereas IL-10 had no effect on them. Although IL-10 increased serum IL-1beta and TNFalpha levels, IL-4 had no effect on them. These findings indicate that the in vitro effects of IL-4 and IL-10 do not necessarily reflect their in vivo effects, and that the complex effects of the two cytokines on serum cytokine levels make it difficult to predict their therapeutic potential.
Tao
M
M
Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison Street, Suite 809, Chicago, Illinois 60612, USA.
Li
B
B
Nayini
J
J
Sivaraman
S
S
Song
S
S
Larson
A
A
Toofanfard
M
M
Chen
H
H
Venugopal
P
P
Preisler
H D
HD
D004999:Amifostine / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000494:pharmacology; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000097:blood / Q000187:drug effects; D019089:Stem Cell Factor / Q000097:blood / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011837:Radiation-Protective Agents; D012795:Sialoglycoproteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004999:Amifostine