In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia

D. T. Scadden, J. D. Levine, J. Bresnahan, J. Gere, J. McGrath, Zack Z. Wang, D. J. Resta, D. Young, S. M. Hammer

Research output: Contribution to journalArticle

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. Design and 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 μg/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-μg/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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)731-740
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume11
Issue number6
StatePublished - 1995
Externally publishedYes

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Interleukin-3
HIV-1
Leukocyte Count
Eosinophils
Hemoglobins
Neutrophils
Blood Platelets
Cutaneous Leukocytoclastic Vasculitis
HIV Core Protein p24
CD4 Lymphocyte Count
Exanthema
Hematocrit
Blood Cells
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
HIV
Cytokines
Safety
Polymerase Chain Reaction
Injections

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Scadden, D. T., Levine, J. D., Bresnahan, J., Gere, J., McGrath, J., Wang, Z. Z., ... Hammer, S. M. (1995). In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia. AIDS Research and Human Retroviruses, 11(6), 731-740.

In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia. / Scadden, D. T.; Levine, J. D.; Bresnahan, J.; Gere, J.; McGrath, J.; Wang, Zack Z.; Resta, D. J.; Young, D.; Hammer, S. M.

In: AIDS Research and Human Retroviruses, Vol. 11, No. 6, 1995, p. 731-740.

Research output: Contribution to journalArticle

Scadden, DT, Levine, JD, Bresnahan, J, Gere, J, McGrath, J, Wang, ZZ, Resta, DJ, Young, D & Hammer, SM 1995, 'In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia', AIDS Research and Human Retroviruses, vol. 11, no. 6, pp. 731-740.
Scadden DT, Levine JD, Bresnahan J, Gere J, McGrath J, Wang ZZ et al. In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia. AIDS Research and Human Retroviruses. 1995;11(6):731-740.
Scadden, D. T. ; Levine, J. D. ; Bresnahan, J. ; Gere, J. ; McGrath, J. ; Wang, Zack Z. ; Resta, D. J. ; Young, D. ; Hammer, S. M. / In vivo effects of interleukin 3 in HIV type 1-infected patients with cytopenia. In: AIDS Research and Human Retroviruses. 1995 ; Vol. 11, No. 6. pp. 731-740.
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AU - Gere, J.

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AU - Resta, D. J.

AU - Young, D.

AU - Hammer, S. M.

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N2 - 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. Design and 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 μg/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-μg/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. Conclusion: 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.

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