Cinque S M S, Rocha G A, Correa-Oliveira R, Soares T F, Moura S B, Rocha A M C, Nogueira A M M F, Cabral M M D A, Vieira L Q, Martins-Filho O A, Queiroz D M M
Laboratório de Pesquisa em Bacteriologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Braz J Med Biol Res. 2006 Feb;39(2):253-61. doi: 10.1590/s0100-879x2006000200012. Epub 2006 Feb 2.
Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma(-/-) C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4(-/-) than in WT BALB/c mice. Serum IFN-gamma levels were significantly higher in IL-4(-/-) than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-gamma levels was seen between H. heilmannii-positive (11.3 +/- 3.07 pg/mL, mean +/- SD) and -negative (11.07 +/- 3.5 pg/mL) WT BALB/c mice, in the group of IL-4(-/-) animals, the serum concentration of IFN-gamma was significantly higher in the infected ones (38.16 +/- 10.5 pg/mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-gamma playing a central role in gastric inflammation.
尽管海氏螺杆菌感染在人类中比幽门螺杆菌感染少见，但因其与胃炎、胃溃疡、胃癌及胃黏膜相关淋巴组织淋巴瘤有关，故被认为具有医学重要性。然而，尚无研究评估Th细胞反应在海氏螺杆菌胃部感染中的作用。我们在基因敲除IFN-γ或IL-4的小鼠中评估了促炎细胞因子IFN-γ和抗炎细胞因子IL-4在海氏螺杆菌胃部感染中的参与情况。通过酶联免疫吸附测定法（ELISA）测定血清IFN-γ和IL-4浓度。海氏螺杆菌阳性的野生型（WT）C57BL/6小鼠的胃多形核浸润高于（P = 0.007）海氏螺杆菌阴性的小鼠，而海氏螺杆菌阳性的IFN-γ(-/-) C57BL/6小鼠的胃中未显示出明显炎症。感染的IL-4(-/-)小鼠胃中炎性细胞的程度，尤其是在胃黏膜中，也高于（P = 0.007）野生型BALB/c小鼠。IL-4(-/-)小鼠的血清IFN-γ水平显著高于野生型BALB/c小鼠，与海氏螺杆菌阳性或阴性状态无关。尽管海氏螺杆菌阳性（11.3±3.07 pg/mL，平均值±标准差）和阴性（11.07±3.5 pg/mL）的野生型BALB/c小鼠之间血清IFN-γ水平无差异，但在IL-4(-/-)动物组中，感染小鼠的血清IFN-γ浓度显著更高（38.16±10.5 pg/mL，P = 0.04）。相反，与海氏螺杆菌阴性（N = 10）的野生型BALB/c动物相比，海氏螺杆菌阳性（N = 10）的动物血清IL-4水平显著降低。总之，海氏螺杆菌感染主要诱导Th1免疫反应，IFN-γ在胃部炎症中起核心作用。
