Anti-interleukin-10 antibody restores burn-induced defects in T-cell function
Anti-interleukin-10 antibody restores burn-induced defects in T-cell function
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DOI：
10.1016/s0039-6060(97)90003-9
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发表时间：
1997-08-01
期刊：
影响因子：
3.8
通讯作者：
Lederer, JA
中科院分区：
文献类型：
--
作者：
Kelly, JL;Lyons, A;Lederer, JA
背景研究表明，严重损伤后对脓毒症的易感性与辅助性T细胞1（Th 1）细胞因子（白细胞介素-[IL-2]和干扰素-γ [IFN-γ]）的产生减少和辅助性T细胞2（Th 2）细胞因子（IL-4和IL-10）的持续存在相关。造成这种影响的机制尚不清楚。我们使用T依赖性抗原来研究烧伤对体内抗原特异性Th功能的影响以及抗IL-10抗体对这些功能的影响。将雄性A/J小鼠麻醉，并给予25%烧伤或假烧伤。在第0天，用100 μ g三硝基苯磺酸（TNP）半抗原化的卵清蛋白（TNP-0 VA）在完全弗氏佐剂中免疫所有小鼠。在第0天给予小鼠（每组10只）250 μ g单克隆大鼠抗尿IL-10抗体（抗IL-10 MAB）或对照大鼠免疫球蛋白G（IgG），在第2天给予100 μ g抗IL-10 MAB或IgG。在第10天，处死小鼠以获得血清和脾细胞。酶联免疫吸附试验（ELISA）测定TNP特异性血清抗体同种型滴度。脾细胞增殖和细胞因子的产生响应TNP-OVA或抗CD 3单克隆抗体测定氚化胸苷掺入和ELISA，respectively.Results，烧伤导致TNP特异性IgG 2a抗体同种型（Th 1依赖）的水平下降，而TNP特异性IgG 1和IgE（Th 2依赖）的水平没有降低烧伤与假烧伤小鼠。抗IL-10 MAB而非IgG恢复了IgG 2a应答。烧伤损伤也导致减少TNP-OVA特异性增殖的脾细胞，而抗CD 3增殖是等效的烧伤和假手术小鼠。TNP-OVA特异性IL-2和IFN-γ的产生显著减少烧伤。抗IL-10单克隆抗体恢复烧伤小鼠脾细胞的TNP-OVA特异性增殖和抗原特异性IL-2和干扰素-γ的产生。烧伤损伤诱导抗原特异性Th 1细胞功能丧失，IL-10作为触发器下调损伤后Th 1活性。
Background. Studies have shown that susceptibility to sepsis after severe injury correlated with reduced production of T-helper 1 (Th1) cytokines (interleukin-[IL-2] and interferon-gamma [IFN-gamma]) and a persistence of T-helper 2 (Th2) cytokines (IL-4 and IL-10). The mechanisms responsible for this effect are not clear. We used a T-dependent antigen to study both the effect of burn injury on antigen-specific Th functions in vivo and the effect of anti-IL-10 antibody on these functions.Methods. Male A/J mice were anesthetized and given a 25 % scald burn or a sham burn. On day 0 all mice were immunized with 100 mu g trinitrobenzene sulfonic acid (TNP) haptenated ovalbumin (TNP-OVA) in complete Freund's adjuvant. Mice (10 per group) were given 250 mu g monoclonal rat antimurine IL-10 antibody (anti-IL-10 MAB) or control rat immunoglobin G (IgG) on day 0 and 100 mu g anti-IL-10 MAB or IgG on day 2. On day 10 the mice were killed to obtain serum and spleen cells. TNP-specific serum antibody isotype titers were determined by enzyme-linked immunosorbent assay (ELISA). Splenocyte proliferation and cytokine production in response to TNP-OVA or to anti-CD3 MAB were determined by tritiated thymidine incorporation and ELISA, respectively.Results, Burn injury resulted in depressed levels of the TNP-specific IgG2a antibody isotype (Th1 dependent), whereas TNP-specific IgG1 and IgE (Th2 dependent) levels were not decreased in burn versus sham burn mice. Anti-IL-10 MAB but not IgG restored the IgG2a response. Burn injury also resulted in reduced TNP-OVA-specific proliferation of splenocytes, whereas anti-CD3 proliferation was equivalent in burn and sham mice. TNP-OVA-specific IL-2 and IFN-gamma production were significantly reduced by burn injury. Anti-IL-10 MAB restored TNP-OVA-specific proliferation and antigen-specific IL-2 and interferon-gamma production by splenocytes from burn mice.Conclusions. Burn injury induces the loss of antigen-specific Th1 cell function, and IL-10 acts as a trigger to down-regulate Th1 activity after injury.