In vitro and in vivo responses to interleukin 12 are maintained until the late SIV infection stage but lost during AIDS

The in vitro proliferative responses of macaque peripheral blood mononuclea r cells (PBMCs) to IL-12 appeared similar before and early after SIV infect ion, whereas macaque PBMCs sampled during symptomatic stages of SIV infecti on showed markedly decreased responses. IL-12 was administered to STVmac239 -infected rhesus macaques either during the asymptomatic or the AIDS stage of infection in efforts to evaluate the effect of this cytokine on immune r esponses, viral loads, and hematopoietic functions in vivo. IFN-gamma secre tion levels induced during the asymptomatic or early symptomatic phase were similar to preinfection induced levels, whereas in later AIDS stages this response was lost, The constitutive levels of other measured cytokines were not affected by IL-12 administration in vivo, The frequency and activity o f circulating NK cells were markedly enhanced at early stages but not at sy mptomatic stages of SIV infection. pCTL frequencies were enhanced at early symptomatic stages but not at late AIDS stages. Despite its immunomodulator y effect, IL-12 did not seem to exacerbate or inhibit the replication of SI V in vivo, or the frequency of circulating infected lymphocytes, IL-12 admi nistration was associated with a significant yet subclinical and transient decrease in hematocrit and hemoglobin levels without evidence of hemolysis, hemodilution, or reduction in the frequency of colony-forming unit potenti al of bone marrow CD34(+) cells. This phenomenon may be explained by a func tional inhibition of differentiation rather than an altered generation of b one marrow precursors. Thus, these results suggest that IL-12 may benefit H IV-1-infected patients only as long as their immune system retains its capa bility to respond to cytokine stimulation.