The Study On The Association Of Interleukin-4, 13 And Their Gene Polymorphisms With Atherothrombotic Cerebral Infarction

Background: Cerebral infarction is a common cerebrovascular diseasewith high disease incidence, morbidity and mortality. Atherosclerosis isone of the main causes of cerebral infarction. It has been known thatinflammation plays a key role in atherosclerosis. Interleukin 4 (IL-4) andIL-13(IL-13) are pleiotropic cytokines exerting similar biological activity.As an anti-inflammation cytokine, the change of IL-4 and IL-13 in braininfarction is controversy. Meanwhile, IL-4 and IL-13 play an importantrole in atherogenesis. There are several genetic polymorphisms locus inIL-4, IL-13 and their receptor which alter their biological activity.Unfortunately, the association of those gene polymorphisms with braininfarction hasn't been reported almost.Part 1The association of IL-4 and IL-13 with atherothrombotic cerebralinfarctionObjects:To be comprehensive understanding the alternation of the IL-4 andIL-13 serum level in the patients with cerebral infarction, the serialchanges of serum IL-4 and IL-13 in atherothrombotic cerebral infarctionpatients will be measured.Methods: A case-control study was carded out in this research, in which28 patients with atherothrombotic cerebral infarction, as well as 151control subjects were recruited. Control subjects with or without carotidartery atherosclerosis were divided into 2 subgroups. 28 cerebralinfarction patients' blood was serially obtained at four times: within 24hours, at day 3, at day 7 and at day 14. The control subjects' blood was collected only once. IL-4 and IL-13 levels in serum samples weredetermined with ELISA method using human IL-4 and IL-13immunoassay kit.Results:1. The serum level of IL-4 was not different among subjects with carotidartery atherosclerosis and no- carotid artery atherosclerosis (P＞0.05).Compared with the control value, the serum IL-4 level obtained at day1 was not increase (P＞0.05). It began to increase at day 3, and peakedat day 7 (3.4 times of control value). The high level of IL-4 lasted today 14(P＜0.01). Meanwhile, the serum levels of IL-4 obtained at day3, 7, and 14 in patients with cerebral infarction were significantlyhigher than the control subjects with carotid atherosclerosis (P＜0.01).2. The serum level of IL-13 was not different among subjects withcarotid artery atherosclerosis and no- carotid artery atherosclerosis(P＞0.05). Compared with the control value, the serum IL-13 levelobtained at day 1 was not increase (P＞0.05). It began to increase atday 3, and peaked at day 7 (2 times of control value). The high levellasted to day 14(P＜0.01). Meanwhile, the serum levels of IL-4obtained at day 3, 7, and 14 in patients with cerebral infarction weresignificantly higher than the control subjects with carotidatherosclerotic (P＜0.01).Conclusion:The serum levels of IL-4 and IL-13 are elevated after cerebralinfarction. This supposes that IL-4 and IL-13 play an anti-inflammationrole in brain ischemic injury and ameliorate brain ischemic injury. Part 2The association of gene polymorphisms of IL-4, IL-13 and IL-4Rwith atherothrombotic cerebral infarctionObjects:1. To elucidate the associations of genetic polymorphism of IL-4 C-590Tand C+33T, IL-13 C+1923T with the serum levels of IL-4 and IL-13.2. To elucidate the associations ofgene polymorphisms of C-590T andC+33T in IL-4, C+1923T in IL-13 and Q576R in IL-4R withatherothrombotic cerebral infarction.Methods: A case-control study was carried out in this research, in which159 patients with atherothrombotic cerebral infarction, as well as 151control subjects were recruited. Genotyping among study subjects wascarried out by polymerase chain reaction (PCR)-restriction fragmentlength polymorphism (RFLP).Results:1. The IL-4 C+33T was in strong linkage disequilibrium with C-590T.The serum IL-4 level in TT genotype was higher than TC and CCgenotype, TC genotype higher than CC genotype. But those genotypesand allele frequencies in IL-4 were found no difference amongpatients with cerebral infarction and control subjects.2. The serum IL-13 level in TT genotype of IL-13 C+1923Tpolymorphism was not different from TC genotype. The serum IL-13level in TT and TC genotype were higher than CC genotype. But thosegenotypes and allele frequencies were found no difference amongpatients with cerebral infarction and control subjects.3. IL-4R Q576R polymorphisms were found no difference amongpatients with cerebral infarction and control subjects. 4. The genotype of IL-4 590T/IL-4R 576R and IL-4 33T/IL-4 576R butnot IL-13 1923T/IL-4R 576R had a significantly increased risk forcerebral infarction.Conclusion:1. IL-4 C+33T is in strong linkage disequilibrium with C-590T. T allelewas associated with high serum IL-4 level. The C-590T and C+33Tpolymorphism are not associated with the risk of atherothromboticcerebral infarction in Chinese Han population.2. The serum IL-13 level depends on IL-13 C+1923T polymorphism, Tallele was associated with high serum IL-13 level. The IL-13C+1923T polymorphism is not associated with the risk ofatherothrombotic cerebral infarction in Chinese Han population.3. The IL-4R Q576R polymorphism is not associated with the risk ofatherothrombotic cerebral infarction in Chinese Han population.4. The genotype of IL-4 590T/IL-4R 576R and IL-4 33T/IL-4 576R arefound to be independent predictors of atherothrombotic cerebralinfarction in Chinese Han population.