Human IL-12 may augment HIV-specific immunity in HIV-positive patients
Promising results of a phase I study suggest that single-dose recombinant human interleukin 12 (rhIL-12) may have therapeutic benefits in HIV-positive patients. Dr Mark A. Jacobson of the University of California at San Francisco and multicenter colleagues examined the effects of a single subcutaneous dose of rhIL-12 in a dose-escalation study. They randomized 47 patients with CD4+ T lymphocyte counts between 100 and 500 cells/µL to doses ranging from 3 ng/mg to 1000 ng/mg or to placebo.
At doses greater than 30 ng/mg, patients demonstrated increases in absolute numbers of CD8+ T lymphocyte cells and natural killer (NK) cells, suggesting an augmentation of HIV-specific immunity. Treatment with rhIL-12 also induced a rise in serum interferon-gamma levels, consistent with earlier studies of the cytokine in both animals and humans. “Of interest, rhIL-12 administration to HIV-positive patients did not change their absolute CD4+ T cell counts or the amount of circulating plasma HIV RNA,” Dr Jacobson’s group writes in the October issue of the Journal of Infectious Diseases. This suggests that a single dose of this agent has no “clinically significant impact either on HIV-induced CD4+ T cell lymphopenia or (via immunomodulation) on HIV replication.” This finding conflicts with earlier reports, the authors note, and may be a result of trial limitations.
Generally mild and transient adverse effects were associated with rhIL-12 doses lower than 300 ng/kg, while severe adverse events occurred at higher doses, particularly the 1000 ng/kg dose. “The immunomodulatory effects of rhIL-12 might be beneficial in HIV disease,” the investigators conclude. Further studies on the effects of rhIL-12 in HIV-positive patients are currently in progress.
J Infect Dis. 2000;182:1070-1076.
Source: Reuters Health