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/ μl and mild splenomegaly) and late‐stage (n=6, CD4+<500/μl, 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.

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