Abstract
Objectives: Interleukin (IL)-12 is a cytokine that stimulates T lymphocytes and natural killer cells to generate a Type 1 T-helper lymphocyte immune response. The primary objective of this study was to determine the safety and immunologic activity of repeated recombinant human IL-12 (rhlL-12) dosing in HIV-infected patients over a broad range of the HIV disease spectrum. Design: A randomized, placebo-controlled, Phase 1 trial design was chosen to control for the effects of HIV disease alone on safety and immunologic measurements. Methods: HIV-infected patients on antiretroviral therapy received rhlL-12 or placebo twice weekly for 4 weeks. Subjects were monitored for safety and changes in absolute lymphocyte subset number, serum interferon (IFN)γ and neopterin levels, plasma HIV RNA level, peripheral blood mononuclear cell (PBMC)-inducible IFNγ responses to mitogen, and PBMC proliferative responses to phytohemagglutinin, tetanus, Candida, Mycobacterium avium complex, streptokinase, and HIV p24 and gp160 antigens. Results: rhlL-12 was well tolerated at doses up to 100 ng/kg in subjects enrolled with CD4 cell counts < 50 × 106 cells/I and at all doses in subjects with CD4 cell counts of 300 × 106-500 × 106 cells/I. rhlL-12 resulted in dose-related increases in serum neopterin (particularly in subjects with baseline CD4 cell counts of 300-500 × 106 cells/I) but in no significant changes in other immunologic measurements or plasma HIV RNA levels. Conclusions: rhlL-12 dosed twice weekly at ≤ 100 ng/kg was well tolerated in HIV-infected patients and resulted in dose-related increases in serum neopterin (possibly reflecting the effect of some degree of IFNγ induction). However, there was no evidence of improvement in antigen-specific immune response.
Original language | English (US) |
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Pages (from-to) | 1147-1154 |
Number of pages | 8 |
Journal | AIDS |
Volume | 16 |
Issue number | 8 |
DOIs | |
State | Published - May 24 2002 |
Externally published | Yes |
Keywords
- AIDS
- Cytokines
- HIV
- Interleukin-12
- T-helper 1
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases