Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection.
The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.
Bucur
S Z
SZ
Department of Pathology, Regional Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Gillespie
T W
TW
Lee
M E
ME
Adams
J W
JW
Bray
R A
RA
Villinger
F
F
Ansari
A A
AA
Hillyer
C D
CD
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D018791:CD4 Lymphocyte Count; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D013926:Thrombopoietin / Q000494:pharmacology*; D019562:Viral Load
D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin