Filgrastim (r-metHuG-CSF) doubled CD4 counts in normal volunteers and restored in vitro IL-2 release in HIV patient blood

Filgrastim, recombinant human granulocyte-colony stimulating factor (G-CSF), induces the proliferation and differentiation of neutrophil precursors. We previously reported reduced formation of the lymphokine IFNγ in blood from Filgrastim-treated volunteers. Consequently, we wanted to determine the effect of Filgrastim on lymphocyte function in healthy volunteers and HIV-infected patients. Twenty-four healthy volunteers were randomized to receive Filgrastim (75, 150, or 300 μg/kg/day) or placebo for 12 days. Blood samples were taken daily and assayed for IL-2 production and lymphocyte proliferation in response to anti-CD3 antibodies (OKT-3), phytohemagglutimn (PHA), or Staphylococcal enterotoxin B (SEB). Blood samples were also collected from 32 HIV-infected patients not receiving Filgrastim, as well as 8 normal volunteers and 8 subjects at high-risk for HIV infection; the blood was stimulated with SEB in the presence or absence of Filgrastim (100 ng/mL). Volunteers receiving Filgrastim showed a transient lymphocytosis with a doubling of CD4+ cells by day 8. Twenty-four hours after the first injection of Filgrastim, ex vivo IL-2 release by stimulated whole blood or mononuclear cells was increased by 110%, p = 0.02; and lymphocyte proliferation was augmented in response to PHA or OKT-3 by 50%, p =0.04. Whole blood from patients with advanced HIV infection showed reduced IL-2 release in the presence of SEB. Reduced in vitro IL-2 production was improved from 160±40, no Filgrastim; to 360±130 pg IL-2/mL with added Filgrastim, p = 0.04. Filgrastim transiently increased the numbers of CD4+ lymphocytes in normal volunteers and in vitro improved SEB induced IL-2 release in the blood of HIV patients. In addition to the effects of Filgrastim to improve neutropenia, this study provides novel data to support additional in vivo studies to determine the effects of Filgrastim on lymphocytes in HIV patients.