Hematologic and virologic effects of lineage-specific and non-lineage-specific recombinant human and rhesus cytokines in a cohort of SIVmac239-infected macaques.
AIDS Res Hum Retroviruses
; 14(8): 651-60, 1998 May 20.
Article
in En
| MEDLINE
| ID: mdl-9618076
ABSTRACT
The hematologic abnormalities of SIV and HIV are well described, although the mechanisms that lead to hematopoietic dysfunction are yet to be fully defined. A number of growth factors and cytokines have been used to induce the differentiation, maturation, and proliferation of appropriate lineages, with the aim that such therapy will lead to functional hematopoietic reconstitution. Within this context, some cytokines have been shown to influence HIV and SIV replication in vitro and, in selected cases, in vivo. However, few studies detail the effects of hematopoietic cytokines such as IL-3, Flt-3 ligand, G-CSF, Tpo, and Epo or correlate the effects on virus replication. In an effort to address this issue, we infected 12 rhesus macaques with 500 TCID50 of SIVmac239 and intensively evaluated hematologic, virologic, and immunologic parameters during administration of cytokines. When all animals had lymphadenopathy, hepatosplenomegaly, and CD4+ cell counts > or =1000/microl, subgroups of three rhesus macaques were administered either rhFlt-3; rrIL-3a; combination of rhG-CSF, rhTpo, and rhEpo (rhGET); or rrIL-12. Fourteen days of rhFlt-3 administration induced expansion of the bone marrow CD34+ cells and granulocyte-macrophage colony-forming units (GM-CFUs) and increased absolute peripheral blood CD34+ cells and total CFUs. Following rrIL-3 and rhGET administration absolute peripheral blood CD34+ cells and total CFUs increased. rhGET also increased granulocyte, platelet, and reticulocyte counts by day 14 of administration. Branched DNA and coculture assays did not demonstrate any significant change in viral load with any of the cytokines administered. These data suggest that SIV-infected rhesus macaques have the hematopoietic capability to expand and mobilize CD34+ and GM-CFU progenitors and formed elements at 6-8 months postinfection in response to various cytokines, without increasing viral load.
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Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Simian Acquired Immunodeficiency Syndrome
/
Growth Substances
Type of study:
Risk_factors_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
AIDS Res Hum Retroviruses
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
1998
Type:
Article
Affiliation country:
United States