Abstract
Objective
Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy.
Methods
One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type −1082 G/A and −819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants.
Results
Compared with control subjects and patients with negative-specific IgE, there were significantly lower levels of IL-10 in patients with positive-specific IgE (P < 0.05). Similarly, there were significantly lower levels of IL-10 in patients with positive-specific IgG compared with normal controls and allergic patients with negative-specific IgG (P < 0.05). The visible negative correlations existed between IL-10 and four types of specific IgE [benzylpenicilloyl (BPO), phenoxomethylpenicilloyl (PVO), benzylpenicillanyl (BPA), amoxicillanyl (AXA)], and patients with three or more positive-specific IgE had significantly lower IL-10 levels than normal controls (P < 0.01). There was a declining trend for IL-10 level in serum with the increase in types of positive-specific IgE. But there was no significant difference in serum IL-10 level between the positive skin-test group and the allergic-history group. Compared with controls and patients with negative antibodies, a significantly decreased frequency of the −1082 G allele was present in patients with positive antibodies (P < 0.01). The allele T and TT genotype at −819 C/T position had lower frequency in the negative-specific IgG group than that in the positive group and controls (P < 0.01).
Conclusions
Positive specific IgE and IgG are associated with decreased IL-10 level in allergic reaction to penicillins. The distributions of genotype and frequency of allele at the −1082 G/A position may be associated with the production of both specific IgE and IgG antibodies.
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References
Mori JC, Pires MC, Galvao CE et al (2001) Determination of Blomia tropicalis-specific IgE and IgG subclasses in atopic dermatitis patients. Allergy 56:180–184
Qiao HL, Yang J, Zhang YW (2005) Relationships between specific serum IgE, cytokines and polymorphisms in the IL-4, IL-4Ra in patients with penicillins allergy. Allergy 60:1053–1059
Punnonen J, de Waal Malefyt R, van Vlasselaer P et al (1993) IL-10 and viral IL-10 prevent IL-4 induced IgE systhesis by inhibiting the accessory cell function of monocytoes. J Immunol 151:1280–1289
Beebe A, Cua D, de Waal Malefyt R (2003) The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev 13:403–412
Moore KW, de Waal Malefyt R, Coffman RL et al (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765
Nakashima I, Fujihara K, Misu T et al (2000) Significant correlation between IL-10 levels and IgG indices in the cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 111:64–67
Perrin GQ, Johnson HM, Subramaniam PS (1999) Mechanism of interleukin-10 inhibition of T-helper cell activation by superantigen at the level of the cell circle. Blood 93:208–216
Wosinska-Becler K, Plewako H, Hakansson L et al (2004) Cytokine production in peripheral blood cells during and outside the pollen season in birch-allergic patients and non-allergic controls. Clin Exp Allergy 34:123–130
Moraes MO, Pacheco AG, Schonkeren JJ et al (2004) IL-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy. Genes Immun 5:592–595
Asseman C, Mauze S, Leach MW et al (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190:995–1004
Keystone E, Wherry J, Grint P (1998) IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am 24:629–639
Ghoreschi K, Mrowietz U, Rocken M (2003) A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J Mol Med 81:471–480
Mageed R, Prud’homme GJ (2003) Immunopathology and the gene therapy of lupus. Gene Ther 10:861–874
Steinke JW, Barekzi E, Hagman J et al (2004) Functional analysis of -571 IL-10 promoter polymorphism reveals a repressor element controlled by Sp1. J Immunol 173:3215–3222
Sumikawa H, Suzuki E, Fukuhara K et al (1998) Dynamic structures of granulocyte colony-stimulating factor proteins studied by normal mode analysis: two domain-type motions in low frequency modes. Chem Pharm Bull (Tokyo) 46:1069–1077
Opdal SH, Opstad A, Vege A et al (2003) IL-10 Gene polymorphisms are associated with infectious cause of sudden infant death. Hum Immunol 64:1183–1189
Breen EC, Boscardin WJ, Detels R et al (2003) Non-Hodgkin’s B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the IL10 promoter −592 C/C genotype. Clin Immunol 109:119–129
Qiao HL, Yang J, Zhang YW (2004) Specific serum IgE levels and FcɛRIβ genetic polymorphism in patients with penicillins allergy. Allergy 59:1326–1332
Zhao ZJ, Batley M, D’Ambrosio C et al (2000) In vitro reactivity of penicilloyl and penicillanyl albumin and polysine conjugates with IgE-antibody. J Immunol Methods 242:43–51
Zhang L, Wang YM, Shen G et al (1996) Enzyme linked immunosorbent assay for detection of IgG agaist penicillins in children. Acta Pharmac Sin 17:274–277
Perrey C, Turner SJ, Pravica V et al (1999) ARMS-PCR methodologies to determine IL-10, TNF-α, TNF-β and TGF-β1 gene polymorphisms. Transpl Immunol 7:127–128
Yang J, Qiao HL, Dong ZM (2005) Polymorphisms of IL-13 and IL-4-IL-13-SNPs in patients with penicillin allergies. Eur J Clin Pharmacol 61(11):803–809, Dec
Qiao HL, Liu JH, Yang J, Dong ZM (2005) Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy. Int J Clin Pract 59:895–899
Suzuki A, Hanada T, Mitsuyama K et al (2001) CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J Exp Med 193:471–481
Alexander WS (2002) Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol 2:410–416
Burdin N, Van Kooten C, Galibert L et al (1995) Endogenous IL-6 and IL-10 contribute to the differentiation of CD40-activated human B lymphocytes. J Immunol 154:2533–2544
Makela MJ, Kanehiro A, Borish L et al (2000) IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proc Natl Acad Sci USA 97:6007–6012
Herrick C, Bottomly K (2003) To respond or not to respond: T cells in allergic asthma. Nat Rev Immunol 3:405–412
Ishida H, Muchamuel T, Sakaguchi S et al (1994) Continuous administration of anti-IL-10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179:305–310
Rosenwasser LJ, Borish L (1997) Genetics of atopy and asthma: the rationale behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med 156:S152–S155
Mocellin S, Marincola F, Rossi CR et al (2004) The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle. Cytokine Growth Factor Rev 15:61–76
Turner DM, Williams DM, Sankaran D et al (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8
Sehra S, Pynaert G, Tournoy K et al (2003) Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma. J Immunol 15:2080–2089
Acknowledgements
We thank Professor B.A. Baldo and Doctor Z.J. Zhao (Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia) for their excellent technical assistance. This project was supported by the Science Foundation for Distinguished Young Scholars of Henan Province (No. 0312002100) and the Engineering Project for Innovative Scholars of Henan Province (No. 2002114).
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Qiao, HL., Wen, Q., Gao, N. et al. Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients. Eur J Clin Pharmacol 63, 263–269 (2007). https://doi.org/10.1007/s00228-006-0245-5
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DOI: https://doi.org/10.1007/s00228-006-0245-5