Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys.
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.
Watanabe
N
N
Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Sypek
J P
JP
Mittler
S
S
Reimann
K A
KA
Flores-Villanueva
P
P
Voss
G
G
Lord
C I
CI
Letvin
N L
NL
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D019562:Viral Load
D000998:Antiviral Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma