Interleukin-10 inhibits in vitro hematopoietic suppression and production of interferon-gamma and tumor necrosis factor-alpha by peripheral blood mononuclear cells from patients with aplastic anemia.
BACKGROUND
Mononuclear cells (MNC) from patients with aplastic anemia (AA) can inhibit hematopoietic colony formation from normal bone marrow (BM) cells. Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are considered as soluble mediators of BM suppression in AA. Because of its cytokine synthesis inhibiting action, interleukin-10 (IL-10) could be a potentially useful molecule to modulate the hematopoietic effects of MNC from patients with AA.


METHODS
Using coculture experiments we studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro hematopoietic suppression by peripheral blood (PB) MNC from AA patients.


RESULTS
PBMNC (5 x 10(5)/ml) from seven patients with AA caused a 40-100% reduction of normal burst-forming unit-erythroid (BFU-E) growth and a 38-91% reduction of colony-forming unit-granulocyte/macrophage (CFU-GM) growth, respectively, in semisolid cocultures. IL-10 was highly effective in reversing growth inhibition in these cocultures. Addition of 10 ng/ml IL-10 to cocultures significantly restored growth of BFU-E in all seven cases and growth of CFU-GM in five of seven cases, respectively. The effect was dose dependent and correlated with decreased IFN-gamma and TNF-alpha production in suspension cultures. Using intracellular cytokine staining it was found that increased TNF-alpha production in AA cells was derived from both CD4+ and CD8+ cells, whereas aberrant IFN-gamma synthesis was only detected in CD8+ cells.


CONCLUSIONS
IL-10 is effective in reversing in vitro hematopoietic suppression by PBMNC from AA patients. These results suggest therapeutic evaluation of rhIL-10 in patients with AA.
Division of Hematology, University of Vienna, Vienna, Austria. klaus.geissler@akh-wien.ac.at
Klaus
K
Geissler
Eva
E
Kabrna
Marietta
M
Kollars
Leopold
L
Ohler
Andrea
A
Berer
Heinz
H
Burgmann
Stefan
S
Winkler
Martin
M
Willheim
Wolfgang
W
Hinterberger
Klaus
K
Lechner
D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma