n-3多不饱和脂肪酸影响炎症及免疫分子机制研究进展

细胞培养、动物实验、临床实验都有证据表明 ,n 3多不饱和脂肪酸或鱼油的补充能改善一些免疫性疾病 ,抑制炎症反应。其机制包括 :n 3多不饱和脂肪酸 (EPA、DHA )能置换细胞膜磷脂中的花生四烯酸 (AA ,n 6 ) ,竞争环氧酶和脂氧合酶从而减少来源于AA的炎性介质 ,减轻炎症反应 :n 3多不饱和脂肪酸也可通过改变细胞膜磷脂脂肪酸构成来影响细胞膜流动性 ,膜上相关信号分子、酶、受体的功能 ,从而改变信号转导过程。此外 ,通过影响酶或细胞因子的基因表达、抑制促炎症因子产生、调节黏附分子表达来调节免疫功能 ,这种机制可不依赖类二十烷酸物质的产生。鱼油中富含的EPA(C2 0∶5,n 3)和DHA (C2 2∶6,n 3)抑制炎症和免疫的作用最为显著。     

血管活性肠肽免疫调节作用的研究进展

血管活性肠肽(VIP)是一种广泛分布的神经肽,其作为信号分子在神经-内分泌-免疫网络中扮演着重要的角色,在免疫系统中,VIP被认为能够通过调节固有免疫和适应性免疫来发挥内源性的免疫调节作用,其能抑制巨噬细胞的促炎反应,调节Th2/Th1的平衡,并促进调节性T细胞的生成,抑制Th17细胞效应,在炎症动物模型如胶原诱导的关节炎、自身免疫性脑脊髓炎中都起到明显作用。现就近年来有关血管活性肠肽的免疫调节机制进行综述,以增进对血管活性肠肽发挥抗炎作用的理解。     

066 共轭亚油酸的免疫调节研究进展

多不饱和脂肪酸具有广泛的生物学功能,其中n-3和n-6系多不饱和脂肪酸对免疫细胞的增殖,T细胞和自然杀伤细胞的活化,细胞因子的产生及免疫应答具有不同的调节作用,共轭亚油酸的发现为多不饱和脂肪酸的研究增添了新的内容.本文结合n-3,n-6系多不饱和脂肪酸的免疫调节作用,综述了近年来成为研究热点的共轭亚油酸的免疫调节作用研究进展情况.     

脂氧素在疾病中的作用

脂氧素( lipoxins,LXs)为花生四烯酸代谢产物,是体内最重要的内源性脂质抗炎介质之一,它参与多种疾病的病理生理过程,在炎症消退及免疫调节过程中发挥至关重要的作用.深入研究LXs的生物学活性及相关机制,可为人类难治性疾病防治提供新的策略和途径.     

11β-HSD1在炎性反应、肝癌的发生发展与免疫中作用的研究进展

11β-羟基类固醇脱氢酶1(11β-HSD1)在与代谢有关的炎性疾病，以及免疫中可通过调节糖皮质激素(GC)的合成发挥抗炎或促炎作用。11β-HSD1的整体表达和活性可受促炎细胞因子的诱导，这一过程依赖于NF-κB信号通路并由其基因(HSD11B1)P1和P2启动子的利用水平最终决定。此外，11β-HSD1在肝细胞癌中通过降低葡萄糖摄入和糖酵解抑制肝细胞癌的增殖，并通过调节GC的水平参与胸腺中T细胞的发育和血管生成。了解11β-HSD1在炎性疾病、癌的发生发展、免疫中的分子调控机制有利于探究相关疾病的发生发展。     

诱导血红素加氧酶-1表达在器官移植中的保护作用

器官移植术中及术后移植器官的缺血再灌注损伤(ischemia-repeffusion injury,IRI)和免疫排斥反应一直困扰着外科医生.血红素加氧酶-1(heme oxygenase-1,HO-1)是血红素代谢过程中的限速酶,广泛分布于哺乳动物的各种组织细胞中.血红素在它的催化下降解代谢为一氧化碳(CO)、胆绿素和游离铁离子.HO-1在氧化应激、炎性反应、低氧和缺血等状态下均能高度表达.HO-1及其催化血红素代谢产物主要通过抗炎性反应、抗氧化反应、调节同种异体反应性T细胞的活性及增殖、抗内皮细胞凋亡、抑制内皮细胞活化等作用机制,对移植器官起到抗IRI和抗免疫排斥作用,从而增加移植器官成活率及延长其存活时间.     

共轭亚油酸的免疫调节研究进展

多不饱和脂肪酸具有广泛的生物学功能，其中n-3和n-6系多不饱和脂肪酸对免疫细胞的增殖，T细胞和自然杀伤细胞的活化，细胞因子的产生及免疫应答具有不同的调节作用，共轭亚油酸的发现为多不饱和脂肪酸的研究增添了新的内容。本文结合n-3，n-6系多不饱和脂肪酸的免疫调节作用，综述了近年来成为研究热点的共轭亚油酸的免疫调节作用研究进展情况。     

糖皮质激素在免疫-炎症中作用机制的研究进展

经典的内分泌负反馈控制回路已不能解释糖皮质激素在免疫性炎症中的广泛作用.外源性糖皮质激素可抑制整个免疫炎症反应,包括促炎因子的表达,T细胞的激活,粘附分子的表达,细胞迁移与效应分子的生成等;内源性糖皮质激素以一种双相、浓度依赖性的方式调节免疫-炎症系统.具有多样促炎特性的细胞因子巨噬细胞迁移抑制因子(MIF)被认为是糖皮质激素诱导性的,该结果可用于解释内源性糖皮质激素双向调节炎症反应的重要特性.     

前B细胞集落增强因子在炎症相关性疾病中的作用

人类前B细胞集落增强因子(pre-B-cell colony-enhancing factor,PBEF)首先被作为一种能够促进前B细胞集落形成的分子而被发现.近年来对PBEF的大量研究显示,PBEF在炎症与免疫、氧化应激、细胞凋亡和糖脂代谢等多种病理生理过程中发挥作用.PBEF在炎症中的作用可能通过其促炎细胞因子活性...     

大承气汤治疗大鼠内毒素性ARDS的疗效分析及免疫调节机制研究

目的： 探讨大承气汤对内毒素“二次打击”致急性呼吸窘迫综合征（ARDS）的防治作用,为中西医结合防治呼吸道疾病提供有效依据。方法: 48只健康雄性Wistar大鼠随机分为4组:生理盐水对照组、ARDS模型组、大承气汤治疗组、地塞米松治疗组,每组12只。采用大肠杆菌脂多糖(LPS) “二次打击”建立大鼠ARDS动物模型,结合动脉血气分析、肺湿/干重(W／D)比值及肺组织病理学观察和评分,评价大承气汤的药理作用;酶联免疫吸附法（ELISA）测定血浆与支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-10水平,探讨大承气汤的药理作用和免疫调节机制。结果: (1)大承气汤可以显著提高ARDS大鼠动脉血氧分压,增加血氧饱和度,降低肺湿/干重比值和肺病理损伤,减轻肺水肿和肺部炎症反应,因而具有改善肺通气、抑制肺部炎症反应、减轻肺损伤功能。(2)大承气汤可使血浆促炎细胞因子（TNF-α、IL-1）和抗炎细胞因子（IL-10）水平同时降低,使BALF中TNF-α、IL-1水平降低同时IL-10水平却升高,因而表现出对全身炎症反应和局部炎症反应不同的免疫调节机能。结论: 大承气汤抑制肺部炎症反应除与下调全身炎症反应水平有关,同时还与促进肺部抗炎介质产生、调节肺部促炎介质/抗炎介质的平衡有关。     

n-3多不饱和脂肪酸在预防皮肤光老化中的作用

目的探讨n-3多不饱和脂肪酸(n-3 PUFA)在预防皮肤光老化中的作用。 方法将8月龄雌性C57BL/6小鼠按照随机数字表法分成2组,n-3 PUFA组和对照组。n-3 PUFA组小鼠除正常饮食外,每日喂食100 μL富含n-3 PUFA [18%二十碳五烯酸(EPA)和12%二十二碳六烯酸(DH)]的鱼油,喂食1个月后对小鼠背部进行脱毛,再以最小红斑剂量的紫外线B对小鼠进行(70 mJ/cm²)照射处理,每周3次,每次20 s,持续1个月。对照组仅同法照射,不喂食n-3 PUFA。实验结束后观察2组小鼠的背部皮肤变化,包括皮肤黑色素沉积灰度和皮纹宽度;用逆转录-聚合酶链反应对黑色素细胞诱导转录因子(MITF)mRNA表达量进行检测;小鼠背部皮肤组织做切片,再用天狼猩红染液进行染色观察,计算皮肤组织厚度;测量胶原蛋白含量;用实时荧光定量检测炎症巨噬细胞相关因子单核细胞趋化蛋白(MCP)-1和肿瘤坏死因子(TNF)-α的表达,以及胶原蛋白Ⅰ、胶原蛋白Ⅲ、细胞外基质金属蛋白酶(MMP)-2、MMP-9表达。数据比较采用Student′s t检验。 结果n-3 PUFA组小鼠皮肤黑色素沉积灰度值为0.87±0.39,明显低于对照组2.25±0.45,差异有统计学意义(t＝2.28,P<0.05);n-3 PUFA组MITF mRNA表达量为0.89±0.02,也明显低于对照组1.00±0.03,差异有统计学意义(t＝2.33,P<0.05);对照组的皮纹相比n-3 PUFA组更加混乱;n-3 PUFA组皮纹宽度为9.65±0.68,对照组皮纹宽度为14.30±0.73,2组比较差异有统计学意(t＝4.65,P<0.05);经天狼猩红染液染色观察到,n-3 PUFA组的皮肤厚度为(218.40±20.40)×10² μm,明显高于对照组(131.60±15.99)×10² μm,差异有统计学意义(t＝3.35,P<0.05);n-3 PUFA组胶原蛋白含量(13.90±0.99) mg/g,高于对照组(10.45±0.44) mg/g,差异有统计学意义(t＝3.18,P<0.05);n-3 PUFA组胶原蛋白Ⅰ表达量1.29±0.09,高于对照组0.98±0.09,差异有统计学意义(t＝2.19,P<0.05),而2组胶原蛋白Ⅲ表达差异不明显,差异无统计学意义(t＝1.01,P＝0.32)。n-3 PUFA组炎症巨噬细胞相关因子MCP-1和TNF-α的表达为0.74±0.06、0.67±0.06,低于对照组1.00±0.09、1.00±0.06,2组比较差异有统计学意义(t＝2.25、3.51,P值均小于0.05);n-3 PUFA组MMP-2和MMP-9的相对值为0.58±0.04、0.74±0.05,均低于对照组1.00±0.06、1.00±0.05,2组比较差异有统计学意义(t＝5.09、3.24,P值均小于0.05)。 结论n-3 PUFA通过增加胶原蛋白合成、降低巨噬细胞浸润和其表达的MMP来抵抗皮肤光老化,具有潜在临床应用价值。     

Dietary omega-3 polyunsaturated fatty acids reduce IFN-gamma receptor expression in mice.

Enrichment of immune cells in vivo or in vitro with omega-3 polyunsaturated fatty acid (n-3 PUFA) has been reported to diminish their response to interferon-y (IFN-gamma). We hypothesized that the n-3 PUFA-induced hyporesponsiveness to IFN-gamma is mediated, in part, by a reduction in the number of IFN-gamma receptors (IFNGR) expressed on the surface of these cells. To test this hypothesis, we fed mice experimental diets containing low or high amounts of n-3 PUFA. Thioglycollate-elicited peritoneal macrophages (PEC) were collected and tested for binding and internalization of [125I]-labeled recombinant murine IFN-gamma. High n-3 PUFA intake was associated with a significant (n = 2, p < 0.01) reduction in [125I]-IFN-gamma binding without affecting binding affinity (Kd). When studies were performed at 37 degrees C, high n-3 PUFA intake reduced internalization of [125I]-rmIFN-gamma by 20%-30% (n = 2,p < 0.001). Results from flow cytometric analysis of IFNGR-1 expression on the surface of murine splenocytes were in agreement with the binding studies. Further, total cellular IFNGR-1 from PEC and splenocytes was examined via immunoprecipitation and Western blotting. High n-3 PUFA diet was associated with a 50% decline (n = 3-6, p < 0.05) in total IFNGR-1 in both immune cell populations studied. These data suggest that reduced IFNGR expression may be responsible for immune cell hyporesponsiveness to IFN-gamma, which may, in part, explain some of the immunomodulatory and anti-inflammatory effects associated with the consumption of diets high in n-3 PUFA.     

Dietary n-3 polyunsaturated fatty acids suppress splenic CD4(+) T cell function in interleukin (IL)-10(-/-) mice

Our laboratory has demonstrated that down-regulation of proliferation and cytokine synthesis by CD4(+) T cells in mice fed diets rich in n-3 polyunsaturated fatty acids (PUFA) is highly dependent on the involvement of the co-stimulatory molecule, CD28. It has been reported that the inhibitory cytokine interleukin (IL)-10 acts directly on T cells which up-regulate IL-10 receptor (IL-10R) expression following stimulation via CD28 by efficiently blocking proliferation and cytokine production. Thus, it was hypothesized that dietary n-3 PUFA would suppress T cell function through the effects of IL-10. The proliferation of purified splenic CD4(+) T cells activated in vitro with anti-CD3 and anti-CD28 (alphaCD3/CD28) from conventional mice (C57BL/6) fed either a control corn oil (CO)-enriched diet devoid of n-3 PUFA, docosahexaenoic acid (DHA; 22 : 6) or eicosapentaenoic acid (EPA; 20 : 5) for 14 days was suppressed by dietary DHA and EPA. Surprisingly, a similar trend was seen in IL-10 gene knock-out (IL-10(-/-)) mice fed dietary n-3 PUFA. IL-10R cell surface expression was also significantly down-regulated on CD4(+) T cells from both the C57BL/6 and IL-10(-/-) mice fed dietary n-3 PUFA after 72 h of in vitro stimulation with alphaCD3/CD28. Enzyme-linked immunosorbent assay (ELISA) measurements revealed that C57BL/6 mice fed DHA had significantly reduced interferon (IFN)-gamma and IL-10 levels 48 h post-activation. However, CD4(+) T cells from IL-10(-/-) mice fed dietary n-3 PUFA produced significantly greater levels of IFN-gamma than the CO-fed group. Our data suggest that in the absence of IL-10, CD4(+) T cells from n-3 PUFA-fed mice may up-regulate IFN-gamma. Suppressed CD4(+) T cells from n-3 PUFA-fed C57BL/6 mice may use mechanisms other than IL-10 to down-regulate T cell function.     

Unbalanced omega-6/omega-3 ratio in red meat products in China

Dietary meats play a crucial role in human health. The objective of this survey was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty acids (n-6/n-3 PUFA) ratio of fresh red meat (beef and pork) from four cities (Shanghai, Nanjing, Yinchuan and Hohhot) in China. The results showed that the n-6/n-3 PUFA ratio from all the samples ranged from 6 to 23. The total n-6 PUFA concentrations ranged from 290.54 mg/100 g in beef from Nanjing to 1601.48 mg/100 g in pork from Hohhot, whereas the total concentrations of n-3 PUFA ranged from 46.34 mg/100 g in beef from Nanjing to 96.03 mg/100 g in pork from Nanjing. The results indicated that the n-6/n-3 ratio in the red meat from all four regions is unbalanced and is much higher than that (< 5:1) recommended by the WHO/FAO. The total amount of n-3 PUFA was far lower than the required daily dose. Therefore, potential solutions to increase the n-3 PUFA content in meat products or to provide alternative source of n-3 PUFA should be explored.     

High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model

To investigate potential dietary risk factors of Alzheimer's disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-beta (Abeta) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.     

Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy

Background: The increased consumption of n-6 polyunsaturated fatty acids (PUFA) has been shown to coincide with the increased prevalence of atopic diseases. We aimed to investigate whether maternal diet and atopic status influence the PUFA composition of breast milk and the serum lipid fatty acids of infants.
Methods: Maternal diet was assessed by a food questionnaire. The PUFA composition of breast milk obtained at 3 months from 20 allergic and 20 healthy mothers and of their infants' (10 atopic and 10 nonatopic/group of mothers) serum lipids was analyzed.
Results: Although no differences in maternal PUFA intake were observed, the breast milk of allergic mothers contained less γ-linolenic acid (18:3 n-6) than that of healthy mothers. Similarly, atopic infants had less γ-linolenic acid in phospholipids than healthy infants, although n-6 PUFA were elevated in other serum lipid fractions in atopic infants. The serum lipid fatty acids in atopic infants did not correlate with those in maternal breast milk.
Conclusions: Our results suggest that dietary n-6 PUFA are not as readily transferred into breast milk or incorporated into serum phospholipids, but may be utilized for other purposes, such as eicosanoid precursors, in allergic/atopic individuals. Subsequently, high dietary proportions of n-6 PUFA, or reduced proportions of regulatory PUFA, such as γ-linolenic acid and n-3 PUFA, may be a risk factor for the development of atopic disease.     

Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy.

BACKGROUND AND OBJECTIVES: The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention. In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease. METHODS: In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-alpha and IFN-gamma) and total IgE levels were measured and compared between the two groups. Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined. RESULTS: Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes. Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group. There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured. CONCLUSIONS: This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels. Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.     

Various dietary polyunsaturated fatty acids modulate acrylamide-induced preneoplatic urothelial proliferation and apoptosis in mice

To investigate whether various dietary fats affected preneoplatic lesions of urinary tract in acrylamide (ACR)-treated mice. Eighty Kunming mice were initiated with ACR at dose 10 mg/kg bw, and fed with different polyunsaturated fatty acid (PUFA): 6% fish oil (enriched in n-3 PUFA), 6% corn oil (enriched in n-6), 6% olein (enriched in n-9, an EFA deficiency inducer), 10% fish oil, 10% corn oil, 10% olein and a commercial chow. Animals were autopsied 22 weeks. The liver fatty acid profile showed a close correlation with dietary sources, exhibiting macroscopic and biochemical EFA-deficient (EFAD) characteristics in ACR mice with olein. The frequency of simple urothelial hyperplasia (H) and dysplasia/carcinoma in situ (D/CIS) was significantly higher in ACR mice with corn oil or olein compared to ACR mice with commercial chow. Proliferation and abnormal luminal localized mitosis, also expression of proliferating cell nuclear antigen (PCNA), significantly increased in ACR mice with corn oil and olein than in ACR mice with commercial chow; moreover, abnormal apoptotic/mitosis ratio, expression of caspase-3, decreased in ACR mice with both olein and corn oil. Fish oil took no significant effect on almost all the parameters in ACR mice in this study. Results suggest that dietary PUFA modulate preneoplastic proliferation in ACR mice; n-6 PUFA (corn oil) and EFAD status (n-9 PUFA) exhibits a promoting activity; whereas, fish oil, rich in n-3 fatty acids, exhibits somewhat attenuated effect, and needs further research.     

Fatty acids in serum cholesteryl esters in relation to asthma and lung function in children

BACKGROUND: Dietary fatty acid intake has been proposed to contribute to asthma development with n-6 polyunsaturated fatty acids (PUFA) having a detrimental and n-3 PUFA a protective effect. OBJECTIVE: The aim of our analysis was to explore the relationship between fatty acid composition of serum cholesteryl esters as marker of dietary intake and prevalence of asthma, impaired lung function and bronchial hyper-responsiveness in children. METHODS: The study population consisted of 242 girls and 284 boys aged 8-11 years, living in Munich, Germany. Data were collected by parental questionnaire, lung function measurement and skin prick test according to the International Study of Asthma and Allergies in Childhood phase II protocol. Confounder-adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association between quartiles of fatty acid concentration and health outcomes with the first quartile as reference. RESULTS: n-3 PUFA: levels of eicosapentaenoic acid were not related to asthma and impaired lung function. Linolenic acid levels were positively associated with current asthma (OR for fourth quartile 3.35, 95% CI 1.29-8.66). Forced expiratory volume in 1 s (FEV(1)) values decreased with increasing levels of linolenic acid (p for trend=0.057). n-6 PUFA: there was a strong positive association between arachidonic acid levels and current asthma (OR(4th quartile) 4.54, 1.77-11.62) and a negative association with FEV(1) (P=0.036). In contrast, linoleic acid was negatively related to current asthma (OR(4th quartile) 0.34, 0.14-0.87) and FEV(1) values increased with increasing levels of linoleic acid (P=0.022). The ratio of measured n-6 to n-3 PUFA as well as levels of palmitic and oleic acid were not consistently related to asthma or lung function. CONCLUSION: Our data do not support the hypothesis of a protective role of n-3 PUFA. Elevated arachidonic acid levels in children with asthma may be because of a disturbed balance in the metabolism of n-6 PUFA or may be secondary to inflammation in these patients.     

N-3 fatty acids modulate Th1 and Th2 dichotomy in diabetic pregnancy and macrosomia

We assessed the implication of Th (helper)-cells and the modulation of the Th1/Th2 dichotomy by n-3 polyunsaturated fatty acids (PUFA) in type I diabetic pregnancy (DP) and macrosomia. Female gestant rats fed a standard diet or n-3 PUFA regimen were rendered diabetic by administration of five low doses of streptozotocin. The macrosomic (MAC) offspring were sacrificed at the age of 90 days. The mRNAs of IL-2 and IFN-gamma (Th1 cytokines) and IL-4 (Th2 cytokine) were downregulated in the pancreas and spleen of diabetic pregnant rats. The levels of IL-10 mRNA, another Th2 cytokine, were unchanged in the spleen or upregulated in the pancreas of these animals. Feeding an n-3 PUFA diet to rats with DP upregulated IL-10 mRNA in the pancreas and IL-4 and IL-10 mRNA in the spleen. In MAC offspring, high expression of IL-2 and IFN-gamma mRNA, but not of Th2 cytokines, was observed. The n-3 PUFA diet diminished Th1 mRNA quantities and increased the levels of IL-4, but not of IL-10, mRNA in MAC offspring. Our study shows that DP is associated with a decreased Th1 phenotype and IL-4 mRNA expression in the pancreas and spleen, and an n-3 PUFA diet upregulates Th2 profile. In MAC offspring, the Th1 phenotype is upregulated and an n-3 PUFA diet downregulates this phenomenon.