title: In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia.
abstract: OBJECTIVE
  To determine the safety, tolerance, and hematological and virological effects of the recombinant hematopoietic growth factor interleukin 3 (IL-3) in HIV-1-infected individuals with cytopenia.
  
  
  METHODS
  A phase I single-center trial was conducted with patients in cohorts of three receiving one of four dose levels of self-administered, subcutaneously injected IL-3 (0.5, 1.0, 2.5, or 5.0 micrograms/kg/day). Toxicities, hematological effects, and virological effects were recorded. Viral studies included serum HIV p24 antigen levels, quantitative plasma and peripheral blood mononuclear cell cultures, and quantitative, competitive polymerase chain reaction of patient plasma.
  
  
  RESULTS
  Increases in white blood cell counts (WBC) and absolute neutrophil counts (ANC) were noted at the higher dose levels while absolute eosinophil counts (AEC) increased in all patients. The percent changes in WBC from baseline ranged from 52 to 309 and in ANC from 20 to 262 in the 2.5- and 5.0-micrograms/kg/day groups. The mean AEC change was 17-fold (range, 2- to 59-fold). Hemoglobin, hematocrit, platelets, and CD4 and CD8 counts were generally unaffected although individual patients demonstrated increases in hemoglobin and platelet levels. Toxicities were generally mild, but one patient developed a transient local erythematous rash at the sites of IL-3 injection which pathologically demonstrated hypersensitivity vasculitis. Of note, viral studies did not demonstrate any consistent changes in HIV-1 activity.
  
  
  CONCLUSIONS
  These data demonstrate limited hematological effects of IL-3 monotherapy in HIV-1-infected patients with cytopenia. However, should IL-3 be incorporated into combination cytokine therapies for HIV disease, these data suggest that IL-3 does not enhance in vivo HIV-1 activity.
authors.affiliation: Division of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Scadden
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Bresnahan
authors.forename: J
authors.initials: J
authors.lastname: Gere
authors.forename: J
authors.initials: J
authors.lastname: McGrath
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: D J
authors.initials: DJ
authors.lastname: Resta
authors.forename: D
authors.initials: D
authors.lastname: Young
authors.forename: S M
authors.initials: SM
authors.lastname: Hammer
mesh_terms: D000328:Adult; D001772:Blood Cell Count; D015331:Cohort Studies; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology; D007970:Leukopenia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014776:Virus Cultivation
chemical_list: D016655:HIV Core Protein p24; D007377:Interleukin-3; D012367:RNA, Viral; D011994:Recombinant Proteins