Thomassen M J, Divis L T, Fisher C J
Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Ohio 44195-5038, USA.
Clin Immunol Immunopathol. 1996 Sep;80(3 Pt 1):321-4. doi: 10.1006/clin.1996.0130.
Alveolar macrophages are the primary source of inflammatory cytokine production in the lung. Both site-specific and differentiation-specific factors play a role in cytokine production, and regulation of this activity in alveolar macrophages is distinctly different from that of circulating blood monocytes. Interleukin-10 (IL-10) inhibits the production of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)] and enhances production of interleukin-1-receptor antagonist (IL-1ra) from endotoxin-stimulated human monocytes, but the effect of IL-10 on such activity in alveolar macrophages is unknown. This study was undertaken to determine the effect of recombinant IL-10 on endotoxin-stimulated cytokine production by human alveolar macrophages. TNF, IL-1, IL-6, and IL-8 secretions were significantly (P < 0.05) stimulated by endotoxin [lipopolysaccharide (LPS)] and were all significantly (P < 0.05) inhibited (median inhibition = 43%) by IL-10 (10 ng/ml). In contrast, IL-1ra was not stimulated by LPS and basal levels were not affected by IL-10. LPS also did not significantly elevate alveolar macrophage IL-10 secretion (< 100 pg/ml) and basal levels were undetectable (< 15 pg/ml). This potent inhibitory activity of IL-10 on inflammatory cytokine production by human alveolar macrophages suggests that exogenous IL-10 may be useful in treatment of inflammatory lung diseases such as adult respiratory distress syndrome.
肺泡巨噬细胞是肺中炎性细胞因子产生的主要来源。位点特异性和分化特异性因子均在细胞因子产生中发挥作用，并且肺泡巨噬细胞中这种活性的调节与循环血单核细胞明显不同。白细胞介素-10（IL-10）可抑制炎性细胞因子[肿瘤坏死因子（TNF）-α、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）]的产生，并增强内毒素刺激的人单核细胞中白细胞介素-1受体拮抗剂（IL-1ra）的产生，但IL-10对肺泡巨噬细胞中此类活性的影响尚不清楚。本研究旨在确定重组IL-10对人肺泡巨噬细胞内毒素刺激的细胞因子产生的影响。肿瘤坏死因子、白细胞介素-1、白细胞介素-6和白细胞介素-8的分泌受到内毒素[脂多糖（LPS）]的显著刺激（P<0.05），并且均受到IL-10（10 ng/ml）的显著抑制（P<0.05）（中位抑制率=43%）。相比之下，LPS未刺激IL-1ra，基础水平也不受IL-10影响。LPS也未显著提高肺泡巨噬细胞IL-10的分泌（<100 pg/ml），基础水平检测不到（<15 pg/ml）。IL-10对人肺泡巨噬细胞炎性细胞因子产生的这种强大抑制活性表明，外源性IL-10可能有助于治疗诸如成人呼吸窘迫综合征等炎性肺病。
