Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys

AIDS Res Hum Retroviruses. 1998 Mar 20;14(5):393-9. doi: 10.1089/aid.1998.14.393.


With the demonstration that interleukin 12 can enhance natural killer (NK) cell activity and drive CD4+ lymphocytes toward T helper type 1 (Thl) responses, there is a strong rationale for exploring the use of this cytokine as an immunomodulatory therapy in HIV-1-infected individuals. To assess its potential safety and effects on both immune and virologic aspects of HIV-1 infection, recombinant human IL-12 (rhIL-12) was assessed in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac). The activity of rhIL-12 on rhesus monkey lymphocytes was confirmed with the demonstration that peripheral blood lymphocyte lysis of the NK-sensitive cell line Colo was enhanced by this recombinant cytokine. Further, rhIL-12 was shown to induce interferon-gamma production by rhesus monkey lymphocytes in vitro. Then, in separate studies, two treatment regimens of rhIL-12 were assessed in SIVmac-infected monkeys: a low-dose regimen (0.1 microg/kg, daily for 4 weeks) and a high-dose regimen (2.5 microg/kg, every 3-4 days, for 3 weeks). Both rhIL-12 treatment regimens were well tolerated by these virus-infected animals. The high-dose regimen of rhIL-12 induced transient decreases in circulating lymphocytes in the SIVmac-infected monkeys. Furthermore, no changes in lymphocyte-associated SIVmac DNA or SIVmac plasma RNA levels were seen in the treated monkeys. These studies indicate that short-term treatment with rhIL-12 is well tolerated and causes no measurable changes in virus load in chronically SIVmac-infected rhesus monkeys.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / therapeutic use*
  • Killer Cells, Lymphokine-Activated / immunology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / virology
  • Macaca mulatta
  • RNA, Viral / isolation & purification
  • Recombinant Proteins / therapeutic use
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects*
  • Viral Load


  • Antiviral Agents
  • RNA, Viral
  • Recombinant Proteins
  • Interleukin-12
  • Interferon-gamma