α-干扰素治疗慢性乙型肝炎患者外周血单个核细胞TLR4表达和血清Th1/Th2型细胞因子的变化

The change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy

目的探讨慢性乙型肝炎患者在α-干扰素治疗前后外周血单个核细胞Toll样受体4(TLR4)的表达及血清Thl/Th2型细胞因子水平的变化及其临床意义。方法 50例HBeAg阳性慢性乙型肝炎患者予以普通α-干扰素治疗。在治疗前及治疗后3月和6月,使用流式细胞仪检测外周血单个核细胞表面TLR4表达;采用ELISA法检测血清IFN-γ和IL-4水平,并同时检测ALT、HBV DNA水平。结果在治疗3个月和6个月时,早期应答组和无应答组患者血清IFN-γ水平均升高,IL-4水平均降低;两组TLR4水平较治疗前均下降,但应答组患者TLR4下降更明显,有显著性差异(P<0.05);IFN-γ和IL-4的变化与TLR4的变化无明显相关(P均>0.05),TLR4与ALT呈正相关(r=0.78,P<0.01),TLR4的变化与HBV DNA变化无相关(P>0.05)。结论在干扰素-α治疗后,慢性乙型肝炎患者Thl/Th2型细胞因子的变化可能与TLR4表达的变化无相关,而对干扰素治疗的疗效可能与TLR4表达的变化有关。

Objective To investigate the change of toll-like receptor 4 on peripheral blood mononuclear cells and the serum Thl/Th2 cytokine levels in patients with chronic hepatitis B receiving interferon-α therapy.Methods 50 patients with chronic hepatitis B were treated with interferon α for six months.After 12 weeks,they were devided into response and non-response group.Serum HBV DNA was detected by PCR;The Thl/Th2 cytokines were measured by ELISA;TLR4 was measured by flow cytometry.Results The IL-4 and TLR4 contents in the two groups at 3rd and 6th month were significantly lower than that before interferon-α therapy（P〈0.05）,while serum IFN-γ levels were higher than that before interferon therapy（P〈0.05）;The levels of IFN-γ,IL-4,TLR4,HBV DNA and ALT at 3rd month were significantly different between the two groups（P〈0.05）;The levels of IFN-γ and IL-4 in 50 patients were not correlated with TLR4 level（P〈0.05）;The change of TLR4 level in response patients at 3rd month was not correlated with the change of HBV DNA levels（P〉0.05）.Conclusions The changes of IFN-γ and IL-4 level in CHB patients received 12 week interferon-α therapy may be not releted to the changes of TLR4 level;the changes of TLR4 level probably is releted to the early response in CHB patients received interferon-α therapy.