Meloni Federica, Caporali Roberto, Marone Bianco Alessia, Paschetto Enrica, Morosini Monica, Fietta Anna Maria, Patrizio Vitulo, Bobbio-Pallavicini Francesca, Pozzi Ernesto, Montecucco Carlomaurizio
Department of Haematological, Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia and IRCCS, Policlinico San Matteo, Pavia, Italy.
Sarcoidosis Vasc Diffuse Lung Dis. 2004 Jun;21(2):111-8.
Fibrosing alveolitis develops in up to 80% of systemic sclerosis patients (SSc) but progression to end stage fibrosis occurs in about 15% of cases. Mechanisms leading to the process remain mostly unknown. We compared cytokine profiles of broncho-alveolar lavage fluids (BAL-f) from patients with SSc associated interstitial lung disease (SSc-ILD) (n. 34), idiopathic pulmonary fibrosis (IPF) (n. 13), stage II sarcoidosis (n. 14) and 9 controls.
Interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), gamma-interferon (IFN-gamma), IL12, IL18 and IL10 and transforming growth factor-beta (TGF-beta) were assessed by ELISA in concentrated BAL-f.
Levels of IL8 and MCP-1 were significantly elevated in SSc-ILD and in IPF as compared with controls (Mann Whitney test p < 0.05), while MCP-1 values were significantly lower in SSc-ILD than in IPF. A significant correlation between neutrophils and IL8 levels (p = 0.047), as well as between eosinophils and MCP-1 levels (p = 0.004) was also observed. IFN-gamma levels were slightly higher than normal only in sarcoidosis (p = 0.06), whereas IL12 levels increased both in sarcoidosis and SSc-ILD (p < 0.05). No differences were found in IL18 and TGF-beta levels. Finally, IL10 levels were higher in SSc-ILD and sarcoidosis than in controls and IPF (p < 0.05).
BAL-f cytokine profile differentiates ILD associated with SSc from IPF. The lower expression of MCP-1 and the higher expression of the anti-fibrotic IL12 and the anti-inflammatory IL10, observed both in sarcoidosis and in SSc-ILD, could account for the better prognosis of these ILDs. Further longitudinal studies are required to confirm whether a different cytokine phenotype may be considered predictive of clinical outcome in SSc-ILD.
高达80%的系统性硬化症(SSc)患者会发生肺纤维化肺泡炎,但约15%的病例会进展至终末期纤维化。导致该过程的机制大多仍不清楚。我们比较了系统性硬化症相关间质性肺疾病(SSc-ILD)患者(34例)、特发性肺纤维化(IPF)患者(13例)、II期结节病患者(14例)及9名对照者的支气管肺泡灌洗液(BAL-f)中的细胞因子谱。
通过酶联免疫吸附测定法(ELISA)对浓缩的BAL-f中的白细胞介素(IL)8、单核细胞趋化蛋白1(MCP-1)、γ干扰素(IFN-γ)、IL12、IL18、IL10及转化生长因子-β(TGF-β)进行评估。
与对照者相比,SSc-ILD和IPF患者的IL8和MCP-1水平显著升高(曼-惠特尼检验,p<0.05),而SSc-ILD患者的MCP-1值显著低于IPF患者。同时还观察到中性粒细胞与IL8水平之间存在显著相关性(p = 0.047),以及嗜酸性粒细胞与MCP-1水平之间存在显著相关性(p = 0.004)。仅在结节病中IFN-γ水平略高于正常(p = 0.06),而在结节病和SSc-ILD中IL12水平均升高(p<0.05)。IL18和TGF-β水平未发现差异。最后,SSc-ILD和结节病患者的IL10水平高于对照者和IPF患者(p<0.05)。
BAL-f细胞因子谱可将与SSc相关的间质性肺疾病与IPF区分开来。在结节病和SSc-ILD中均观察到的MCP-1较低表达以及抗纤维化IL12和抗炎IL10的较高表达,可能是这些间质性肺疾病预后较好的原因。需要进一步的纵向研究来确认不同的细胞因子表型是否可被视为SSc-ILD临床结局的预测指标。