van Furth A M, Verhard-Seijmonsbergen E M, van Furth R, Langermans J A
Department of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Immunology. 1997 Jun;91(2):193-6. doi: 10.1046/j.1365-2567.1997.00252.x.
The present study concerns the effect of the xanthine derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL-10) by human leucocytes during stimulation with lipopolysaccharide (LPS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimulated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae was inhibited by both drugs. The production of IL-10 by leucocytes stimulated with LPS and Hib was inhibited by both xanthine derivates only at 48 hr. However, incubation of leucocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four- and twofold at 24 hr and 48 hr, respectively. In all instances, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.
本研究关注黄嘌呤衍生物利索茶碱（LSF）和己酮可可碱（PTX）对人白细胞在受到脂多糖（LPS）、热灭活革兰氏阴性菌（GNB）或革兰氏阳性菌（GPB）刺激时促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）以及失活细胞因子白细胞介素-10（IL-10）产生的影响。两种药物均抑制了由LPS、b型流感嗜血杆菌（Hib）或肺炎链球菌刺激的白细胞产生TNF-α和IL-1β。仅在48小时时，两种黄嘌呤衍生物均抑制了由LPS和Hib刺激的白细胞产生IL-10。然而，在LSF或PTX存在的情况下，白细胞与肺炎链球菌孵育分别在24小时和48小时时刺激IL-10的产生增加约四倍和两倍。在所有情况下，LSF或PTX对细胞因子产生的抑制或增强程度相同。黄嘌呤衍生物对IL-10产生的不同影响表明，根据白细胞是受到GPB还是GNB刺激，存在不同的细胞内途径。
