Kafka Daniel, Ling Eduard, Feldman Galia, Benharroch Daniel, Voronov Elena, Givon-Lavi Noga, Iwakura Yoichiro, Dagan Ron, Apte Ron N, Mizrachi-Nebenzahl Yaffa
Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer Sheva 84101, Israel.
Int Immunol. 2008 Sep;20(9):1139-46. doi: 10.1093/intimm/dxn071. Epub 2008 Jul 1.
The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1alpha-/-, IL-1beta-/-, IL-1alpha/beta-/- and IL-1R antagonist (IL-1Ra)-/- mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1beta-/- and IL-1alpha/beta-/- mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1alpha-/- and IL-1Ra-/- mice. Treatment of IL-1beta-/- mice with rIL-1beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1alpha-/- and IL-1Ra-/- but not in IL-1beta-/- and IL-1alpha/beta-/- mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1alpha-/- and control mice. However, S. pneumoniae-infected IL-1beta-/-, IL-1alpha/beta-/- and IL-1Ra-/- mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1alpha and IL-1beta in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1beta has a major role in resistance to primary pneumococcal infection while the role of IL-1alpha is less important.
在鼻内接种后，对白细胞介素-1（IL-1）家族基因缺陷小鼠（即IL-1α-/-、IL-1β-/-、IL-1α/β-/-和IL-1受体拮抗剂（IL-1Ra）-/-小鼠）中IL-1在肺炎链球菌感染易感性中的作用进行了研究。与对照、IL-1α-/-和IL-1Ra-/-小鼠相比，IL-1β-/-和IL-1α/β-/-小鼠鼻内接种肺炎链球菌后存活率显著降低，鼻咽部和肺部细菌载量更高。用重组IL-1β治疗IL-1β-/-小鼠可显著提高其存活率。在对照、IL-1α-/-和IL-1Ra-/-小鼠中发现血液中性粒细胞显著增加，但在IL-1β-/-和IL-1α/β-/-小鼠中未发现。在IL-1α-/-和对照小鼠的肺部观察到中性粒细胞局部浸润且器官结构相对保留。然而，感染肺炎链球菌的IL-1β-/-、IL-1α/β-/-和IL-1Ra-/-小鼠表现出弥漫性肺炎和组织损伤。总之，所有三种亚型都有助于抵御肺炎链球菌；我们的结果表明IL-1α和IL-1β在肺炎链球菌感染的发病机制和控制中具有不同作用，提示IL-1β在抵抗原发性肺炎球菌感染中起主要作用，而IL-1α的作用不太重要。
