Granowitz E V, Saget B M, Wang M Z, Dinarello C A, Skolnik P R
Department of Medicine, New England Medical Center Hospitals, Boston, MA 02111, USA.
Mol Med. 1995 Sep;1(6):667-77.
Cytokines and cytokine antagonists modulate human immunodeficiency virus (HIV) replication in vitro and may be involved in HIV disease pathogenesis. An understanding of these cytokine networks may suggest novel treatment strategies for HIV-seropositive persons.
U1 cells, a chronically infected promonocytic cell line, were stimulated with interleukin 1 alpha (IL-1 alpha), IL-1 beta or tumor necrosis factor (TNF) for 24 hr. The effects of these cytokines, and of anti-IL-1 receptor type 1 and type 2 (IL-1RI and II) antibody, IL-1 receptor antagonist (IL-1Ra), and recombinant human TNF binding protein type 1 (rhTBP-1, a form of TNF receptor p55), on HIV-1 replication, as measured by ELISA for HIV-1 p24 antigen, were determined. The effects of IL-1 and IL-1Ra on nuclear factor-kappa B (NF-kappa B) DNA binding activity, as measured by electrophoretic mobility shift assays, were also determined.
IL-1 alpha and IL-1 beta increased p24 antigen production in a concentration-dependent manner. IL-1Ra completely, and rhTBP-1 partially, suppressed IL-1-induced p24 antigen production. IL-1 increased NF-kappa B DNA binding activity and IL-1Ra blocked this effect. Since IL-1Ra blocks IL-1 from binding to both the IL-1RI and Il-1RII, monoclonal antibodies directed against each receptor were used to ascertain which IL-1R mediates IL-1-induced HIV-1 expression. Antibody to the IL-1RI reduced IL-1-induced p24 antigen production. Although anti-IL-1RII antibody blocked the binding of 125IL-1-1 alpha to U1 cells by 99%, this antibody did not affect IL-1-induced p24 antigen production. IL-1 beta enhanced TNF alpha-induced HIV expression when added before or simultaneously with TNF alpha.
IL-1 induces HIV-1 expression (via the IL-1RI) and NF-kappa B activity in U1 cells. These effects are blocked by IL-1Ra and partially mediated by TNF. IL-1 enhances TNF alpha-induced HIV replication in U1 cells.
细胞因子和细胞因子拮抗剂在体外可调节人类免疫缺陷病毒（HIV）复制，可能参与HIV疾病的发病机制。了解这些细胞因子网络可能为HIV血清阳性者提示新的治疗策略。
用白细胞介素1α（IL-1α）、IL-1β或肿瘤坏死因子（TNF）刺激慢性感染的原单核细胞系U1细胞24小时。通过ELISA检测HIV-1 p24抗原，确定这些细胞因子以及抗1型和2型IL-1受体（IL-1RI和II）抗体、IL-1受体拮抗剂（IL-1Ra）和重组人TNF结合蛋白1型（rhTBP-1，一种TNF受体p55形式）对HIV-1复制的影响。还通过电泳迁移率变动分析确定IL-1和IL-1Ra对核因子-κB（NF-κB）DNA结合活性的影响。
IL-1α和IL-1β以浓度依赖方式增加p24抗原产生。IL-1Ra完全抑制，rhTBP-1部分抑制IL-1诱导的p24抗原产生。IL-1增加NF-κB DNA结合活性，IL-1Ra阻断此效应。由于IL-1Ra阻止IL-1与IL-1RI和IL-1RII两者结合，因此使用针对每种受体的单克隆抗体来确定哪种IL-1R介导IL-1诱导的HIV-1表达。抗IL-1RI抗体降低IL-1诱导的p24抗原产生。尽管抗IL-1RII抗体使125IL-1-1α与U1细胞的结合阻断99%，但该抗体不影响IL-1诱导的p24抗原产生。当在TNFα之前或同时添加时，IL-1β增强TNFα诱导的HIV表达。
IL-1在U1细胞中诱导HIV-1表达（通过IL-1RI）和NF-κB活性。这些效应被IL-1Ra阻断，部分由TNF介导。IL-1增强U1细胞中TNFα诱导的HIV复制。
