Bayard-McNeeley M, Doo H, He S, Hafner A, Johnson W D, Ho J L
Department of Medicine, Cornell University Medical College, New York 10021, USA.
Clin Diagn Lab Immunol. 1996 Sep;3(5):547-53. doi: 10.1128/cdli.3.5.547-553.1996.
Cytokines may have clinical utility as therapeutic agents for human immunodeficiency virus type 1 (HIV-1) infection and as an adjuvant for vaccines. The effect of interleukin-12 (IL-12) and IL-15 on in vitro HIV-1 replication was investigated. IL-12 and IL-15 at doses up to 10 ng/ml had little effect on basal HIV-1 p24 antigen production by chronically HIV-infected T (ACH-2) and monocytic (U1) cell lines. For ACH-2 cells stimulated with phorbol 12-myristate 13-acetate (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production by 20 and 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml) treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and 15%, respectively (n = 6). We next studied the effect of IL-12 and IL-15 on HIV-infected peripheral blood mononuclear cells (PBMCs). In 10 HIV-seropositive patients' PBMCs cocultured with mitogen-activated HIV-seronegative donor cells, two patterns of p24 antigen production were observed in response to IL-2: low (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production > 10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15 increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and 0.004, respectively). For the high-response pattern, both IL-12 and IL-15 suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in vitro infection by HIV-1JRCSF was also examined. IL-12 did not increase p24 antigen production above basal levels while IL-2 and IL-15 significantly enhanced p24 antigen production (by approximately 2-fold). In conclusion, IL-12 and IL-15 may have differential effects on latent and acute HIV infection, and their ability to enhance HIV production may depend on cell activation. Thus, the use of these cytokines may be dictated by the clinical state of the patient.
细胞因子作为治疗人类免疫缺陷病毒1型（HIV-1）感染的治疗剂和疫苗佐剂可能具有临床应用价值。研究了白细胞介素-12（IL-12）和IL-15对体外HIV-1复制的影响。高达10 ng/ml剂量的IL-12和IL-15对慢性HIV感染的T（ACH-2）和单核细胞（U1）细胞系的基础HIV-1 p24抗原产生几乎没有影响。对于用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA；50 ng/ml）刺激的ACH-2细胞，IL-12和IL-15分别使p24抗原产生显著增加20%和30%（n = 6）。相比之下，用IL-12和IL-15（10 ng/ml）处理PMA刺激的U1细胞，p24抗原产生分别降低了16%和15%（n = 6）。接下来，我们研究了IL-12和IL-15对HIV感染的外周血单核细胞（PBMC）的影响。在10例HIV血清阳性患者的PBMC与丝裂原激活的HIV血清阴性供体细胞共培养中，观察到两种p24抗原产生模式对IL-2的反应：低反应（p24抗原产生<10³ pg/ml；n = 8）和高反应（p24抗原产生>10³ pg/ml；n = 2）。对于低反应模式，IL-12和IL-15分别使病毒复制增加97倍和100倍（P分别为0.05和0.004）。对于高反应模式，IL-12和IL-15均抑制HIV复制。还研究了IL-2、IL-12和IL-15对HIV-1JRCSF急性体外感染的影响。IL-12没有使p24抗原产生增加到基础水平以上，而IL-2和IL-15显著增强了p24抗原产生（约2倍）。总之，IL-12和IL-15对潜伏性和急性HIV感染可能有不同的影响，它们增强HIV产生的能力可能取决于细胞激活。因此，这些细胞因子的使用可能取决于患者的临床状态。
