Single Nucleotide Polymorphism and Production of IL-1β and IL-10 Cytokines in Febrile Seizures

B.G. Nur; D. Sahinturk; M. Coskun; O. Duman; U. Yavuzer; S. Haspolat

doi:10.1055/s-0032-1323849

Neuropediatrics, Table of Contents

Neuropediatrics 2012; 43(04): 194-200
DOI: 10.1055/s-0032-1323849

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Single Nucleotide Polymorphism and Production of IL-1β and IL-10 Cytokines in Febrile Seizures

B.G. Nur

¹Division of Pediatric Genetics, Department of Pediatrics, Akdeniz University School of Medicine, Antalya, Turkey

,

D. Sahinturk

²Department of Child Immunology, Akdeniz University School of Medicine, Antalya, Turkey

,

M. Coskun

²Department of Child Immunology, Akdeniz University School of Medicine, Antalya, Turkey

,

O. Duman

³Division of Pediatric Neurology, Department of Pediatrics, Akdeniz University School of Medicine, Antalya, Turkey

,

U. Yavuzer

⁴Department of Physiology, Akdeniz University School of Medicine, Antalya, Turkey

,

S. Haspolat

³Division of Pediatric Neurology, Department of Pediatrics, Akdeniz University School of Medicine, Antalya, Turkey

› Author Affiliations

Abstract

Inflammation and genetics may play a role in the pathogenesis of febrile seizures. The aim of this study was to investigate the spontaneous and lipopolysaccharide (LPS)-induced production of IL-1β and IL-10, and the association between IL-1β (−511) and IL-10 (−1082) single nucleotide polymorphisms with LPS-induced cytokine production. The study included 92 febrile seizure patients and 132 healthy controls. First, we isolated genomic DNA and by using PCR-RFLP we genotyped the individuals for the cytokines gene polymorphism. Second, peripheral mononuclear cells of the individuals were isolated and stimulated with LPS to measure secretion capacity of IL-1β and IL-10 using specific ELISA kits. We found that both the IL-1β and IL-10 production was increased in febrile seizures. The rapid increase of IL-1β production in the supernatants of the LPS-induced cells was significantly higher at the fourth and the twenty-fourth hours in febrile and complex febrile seizures, respectively. The distribution of IL-10 (−1082) G allele differs significantly between cases and controls. The IL-1β (−511) G/A and the IL-10 (−1082) G/A genotype combination was found to be higher in patients with febrile seizure. Our results showed that IL-1β and IL-10 production was not influenced by the single nucleotide polymorphisms in the pathogenesis of febrile seizures.

Keywords

febrile seizure - cytokine - polymorphism

Full Text

References

References
1 Lennox-Buchthal MA. Febrile convulsions. In: Laidlaw J, Richens A, eds. A Textbook of Epilepsy. New York: Churchill Livingston; 1982: 68-88
2 Berg AT, Shinnar S, Shapiro ED, Salomon ME, Crain EF, Hauser WA. Risk factors for a first febrile seizure: a matched case-control study. Epilepsia 1995; 36 (4) 334-341
3 Nelson KB, Ellenberg JH. Prenatal and perinatal antecedents of febrile seizures. Ann Neurol 1990; 27 (2) 127-131
4 Heida JG, Moshé SL, Pittman QJ. The role of interleukin-1beta in febrile seizures. Brain Dev 2009; 31 (5) 388-393
5 Hopkins SJ, Rothwell NJ. Cytokines and the nervous system. I: expression and recognition. Trends Neurosci 1995; 18 (2) 83-88 . Review
6 Tomoum HY, Badawy NM, Mostafa AA, Harb MY. Plasma interleukin-1beta levels in children with febrile seizures. J Child Neurol 2007; 22 (6) 689-692
7 Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765
8 Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ. Interleukin-1beta contributes to the generation of experimental febrile seizures. Ann Neurol 2005; 57 (1) 152-155
9 Heida JG, Pittman QJ. Causal links between brain cytokines and experimental febrile convulsions in the rat. Epilepsia 2005; 46 (12) 1906-1913
10 Bidwell J, Keen L, Gallagher G , et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 1999; 1 (1) 3-19
11 Kanemoto K, Kawasaki J, Yuasa S , et al. Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia 2003; 44 (6) 796-799
12 Chou IC, Tsai CH, Hsieh YY, Peng CT, Tsai FJ. Association between polymorphism of interleukin-1beta-511 promoter and susceptibility to febrile convulsions in Taiwanese children. Acta Paediatr 2003; 92 (11) 1356
13 Baulac S, Gourfinkel-An I, Nabbout R , et al. Fever, genes, and epilepsy. Lancet Neurol 2004; 3 (7) 421-430
14 Haspolat S, Baysal Y, Duman O, Coşkun M, Tosun O, Yeğin O. Interleukin-1alpha, interleukin-1beta, and interleukin-1Ra polymorphisms in febrile seizures. J Child Neurol 2005; 20 (7) 565-568
15 Virta M, Hurme M, Helminen M. Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures. Pediatr Neurol 2002; 26 (3) 192-195
16 Serdaroglu G, Alpman A, Tosun A , et al. Febrile seizures: interleukin 1beta and interleukin-1 receptor antagonist polymorphisms. Pediatr Neurol 2009; 40 (2) 113-116
17 Chou IC, Lin WD, Wang CH, Tsai CH, Li TC, Tsai FJ. Interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10, and tumor necrosis factor alpha gene polymorphisms in patients with febrile seizures. J Clin Lab Anal 2010; 24 (3) 154-159
18 Tilgen N, Pfeiffer H, Cobilanschi J , et al. Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions. Neurosci Lett 2002; 334 (1) 68-70
19 Helminen M, Vesikari T. Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand 1990; 79 (8-9) 810-816
20 Lahat E, Livne M, Barr J, Katz Y. Interleukin-1beta levels in serum and cerebrospinal fluid of children with febrile seizures. Pediatr Neurol 1997; 17 (1) 34-36
21 Ichiyama T, Nishikawa M, Yoshitomi T, Hayashi T, Furukawa S. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures. Comparison with acute encephalitis/encephalopathy. Neurology 1998; 50 (2) 407-411
22 Tutuncuoglu S, Kütükçüler N, Kepe L, Coker C, Berdeli A, Tekgül H. Proinflammatory cytokines, prostaglandins and zinc in febrile convulsions. Pediatr Int 2001; 43 (3) 235-239
23 Haspolat S, Mihçi E, Coşkun M, Gümüslü S, Ozben T, Yeğin O. Interleukin-1beta, tumor necrosis factor-alpha, and nitrite levels in febrile seizures. J Child Neurol 2003; 18 (2) 118
24 Donnelly S, Loscher C, Mills KH, Lynch MA. Glycerol-induced seizure: involvement of IL-1beta and glutamate. Neuroreport 1999; 10 (9) 1821-1825
25 Szaflarski J, Burtrum D, Silverstein FS. Cerebral hypoxia-ischemia stimulates cytokine gene expression in perinatal rats. Stroke 1995; 26 (6) 1093-1100
26 Straussberg R, Amir J, Harel L, Punsky I, Bessler H. Pro- and anti-inflammatory cytokines in children with febrile convulsions. Pediatr Neurol 2001; 24 (1) 49-53
27 Virta M, Hurme M, Helminen M. Increased plasma levels of pro- and anti-inflammatory cytokines in patients with febrile seizures. Epilepsia 2002; 43 (8) 920-923
28 Ishizaki Y, Kira R, Fukuda M , et al. Interleukin-10 is associated with resistance to febrile seizures: genetic association and experimental animal studies. Epilepsia 2009; 50 (4) 761-767
29 Jotanovic Z, Etokebe GE, Mihelic R , et al. Hip osteoarthritis susceptibility is associated with IL1B -511(G > A) and IL1 RN (VNTR) genotypic polymorphisms in Croatian Caucasian population. J Orthop Res 2011; 29 (8) 1137-1144
30 Wu ZQ, Sun L, Sun YH, Ren C, Jiang YH, Lu XL. Interleukin 1 beta -511 C/T gene polymorphism and susceptibility to febrile seizures: a meta-analysis. Mol Biol Rep 2012; 39 (5) 5401-5407