Bienvenu J, Doche C, Gutowski M C, Lenoble M, Lepape A, Perdrix J P
Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Pierre Benite, France.
J Cardiovasc Pharmacol. 1995;25 Suppl 2:S80-4. doi: 10.1097/00005344-199500252-00017.
The modulation of cytokine release induced by pentoxifylline (PTX) has recently been demonstrated not to be restricted solely to tumor necrosis factor (TNF)-alpha. This prompted us to study the influence of PTX on a larger spectrum of cytokines with proinflammatory actions [TNF-alpha, interleukin-6, (IL)-6, IL-1 beta, IL-8] or with implied actions in the TH1 (IL-2, IFN-gamma)/TH2 (IL-10) balance. The IL-1RA was also explored. This work was performed using a whole-blood model in which cytokine production is measured after stimulation by lipopolysaccharide (LPS) (25 micrograms/ml) and phytohemagglutinin (PHA) (5 micrograms/ml) in 1:10 diluted whole blood. The stimulation test was performed in blood from healthy controls and from septic patients (without septic shock) in the presence or absence of PTX at 10(-6), 10(-5), 10(-4), or 10(-3) M. In controls and septic patients, at a 10(-4) M PTX concentration the production of IL-2 is strongly diminished (26-32% of the basal level), followed by diminution of IFN-gamma (30-40%). As expected, of the proinflammatory cytokines TNF was the most strongly suppressed (50% of baseline) followed by IL-1 (about 80% of basal production). Finally, IL-10 was also influenced by PTX (65% of baseline). At 10(-4) M, IL-1RA and IL-6 were unaffected by PTX. Taken altogether, our data demonstrate that PTX possesses a much broader spectrum of activity on cytokine production than was initially described, and it appears to be a potential and promising immunotherapeutic agent.
己酮可可碱（PTX）诱导的细胞因子释放调节作用最近已被证实不仅限于肿瘤坏死因子（TNF）-α。这促使我们研究PTX对更广泛的具有促炎作用的细胞因子 [TNF-α、白细胞介素-6（IL-6）、IL-1β、IL-8] 或在TH1（IL-2、干扰素-γ）/TH2（IL-10）平衡中具有潜在作用的细胞因子的影响。同时也对IL-1受体拮抗剂（IL-1RA）进行了研究。这项工作使用全血模型进行，在1:10稀释的全血中用脂多糖（LPS）（25微克/毫升）和植物血凝素（PHA）（5微克/毫升）刺激后测量细胞因子的产生。在有或没有10⁻⁶、10⁻⁵、10⁻⁴或10⁻³M PTX的情况下，对健康对照者和脓毒症患者（无脓毒症休克）的血液进行刺激试验。在对照者和脓毒症患者中，PTX浓度为10⁻⁴M时，IL-2的产生强烈减少（为基础水平的26%-32%），随后干扰素-γ减少（30%-40%）。正如预期的那样，在促炎细胞因子中，TNF受到的抑制最强（为基线的50%），其次是IL-1（约为基础产生量的80%）。最后，IL-10也受到PTX的影响（为基线的65%）。在10⁻⁴M时，IL-1RA和IL-6不受PTX影响。总体而言，我们的数据表明，PTX对细胞因子产生的活性谱比最初描述的要广泛得多，它似乎是一种潜在且有前景的免疫治疗药物。
