VZV Foundation - A Decade Of Leadership In The Fight Against VZV Infections

	Oral Presentation Abstracts: 40 [40] POLYMORPHISM OF THE INTERLEUKIN-10 GENE IS ASSOCIATED WITH SUSCEPTIBILITY TO HERPES ZOSTER *M.Haanpää (1), T.Nurmikko (2), M.Hurme (3) (1) Department of Neurology, Peijas Hospital, Vantaa, Finland; (2) Pain Research Institute, Department of Neurological Science, University of Liverpool, United Kingdom; (3) Department of Microbiology and Immunology, University of Tampere Medical School, Finland IL-10 is a multifunctional cytokine, which suppresses cell-mediated immunity, stimulates immunoglobulin production, and downregulates the production of the pro-inflammatory cytokines. The promoter region of the IL-10 gene is polymorphic. It contains at least three single nucleotide exchanges, G/A at the position -1082, C/T at the position -819 and C/A at the position -592. Although there might be stimulus or cell type -dependent variations, haplotype GCC seems to be associated with high IL-10 production capacity and ATA with low capacity. We have previously observed that in the case of Epstein-Barr virus, susceptibility to the primary infection as well as its severity are associated with the polymorphism of the promoter region of the IL-10 gene. We now analyzed whether this same gene is involved in the regulation of the immune response against dormant varicella zoster, i.e. whether the genetically determined variations in the IL-10 production would have an effect on susceptibility to herpes zoster (HZ). We analyzed these polymorphisms in 60 HZ patients and in 400 healthy blood donors, who were Varicella zoster (VZ) antibody positive. The HZ patients were immunocompetent and aged 18-83y (mean 61y). The frequency of the carriers of the ATA haplotype was higher among the herpes zoster patients than controls (38% vs. 53%, p<0.05, chi-square test) and this increase was associated with a non-significant decrease in the carrier rates of the two other haplotypes. Correspondingly, the frequency of the ATA haplotype was clearly higher in the patient group (31.7% vs. 22.0 %, p<0.0001, chi-square test). These results indicate that IL-10 is involved in the immune mechanisms keeping the dormant VZV in control. As ATA haplotype is associated with a low IL-10 production capacity, it seems that high concentrations of IL-10 are required for the optimal inhibition of VZV reactivation. Thus it is probable that downregulation of the cell-mediated immunty is not the major function of IL-10 in this case. More likely, IL-10 is required for the effective suppression of production of the proinflammatory cytokines, which, at least in the murine gene knock-out models, are involved in the reactivation of dormant herpesviruses. Corresponding Author: M.Hurme, MD, Professor of Microbiology and Immunology, University of Tampere Medical School, POB 607, FIN-33101 Tampere, Finland

[40]

POLYMORPHISM OF THE INTERLEUKIN-10 GENE IS ASSOCIATED WITH SUSCEPTIBILITY TO HERPES ZOSTER

*M.Haanpää (1), T.Nurmikko (2), M.Hurme (3)
(1) Department of Neurology, Peijas Hospital, Vantaa, Finland; (2) Pain Research Institute, Department of Neurological Science, University of Liverpool, United Kingdom; (3) Department of Microbiology and Immunology, University of Tampere Medical School, Finland

IL-10 is a multifunctional cytokine, which suppresses cell-mediated immunity, stimulates immunoglobulin production, and downregulates the production of the pro-inflammatory cytokines. The promoter region of the IL-10 gene is polymorphic. It contains at least three single nucleotide exchanges, G/A at the position -1082, C/T at the position -819 and C/A at the position -592. Although there might be stimulus or cell type -dependent variations, haplotype GCC seems to be associated with high IL-10 production capacity and ATA with low capacity. We have previously observed that in the case of Epstein-Barr virus, susceptibility to the primary infection as well as its severity are associated with the polymorphism of the promoter region of the IL-10 gene. We now analyzed whether this same gene is involved in the regulation of the immune response against dormant varicella zoster, i.e. whether the genetically determined variations in the IL-10 production would have an effect on susceptibility to herpes zoster (HZ).

We analyzed these polymorphisms in 60 HZ patients and in 400 healthy blood donors, who were Varicella zoster (VZ) antibody positive. The HZ patients were immunocompetent and aged 18-83y (mean 61y). The frequency of the carriers of the ATA haplotype was higher among the herpes zoster patients than controls (38% vs. 53%, p<0.05, chi-square test) and this increase was associated with a non-significant decrease in the carrier rates of the two other haplotypes. Correspondingly, the frequency of the ATA haplotype was clearly higher in the patient group (31.7% vs. 22.0 %, p<0.0001, chi-square test).

These results indicate that IL-10 is involved in the immune mechanisms keeping the dormant VZV in control. As ATA haplotype is associated with a low IL-10 production capacity, it seems that high concentrations of IL-10 are required for the optimal inhibition of VZV reactivation. Thus it is probable that downregulation of the cell-mediated immunty is not the major function of IL-10 in this case. More likely, IL-10 is required for the effective suppression of production of the proinflammatory cytokines, which, at least in the murine gene knock-out models, are involved in the reactivation of dormant herpesviruses.

Corresponding Author: M.Hurme, MD, Professor of Microbiology and Immunology, University of Tampere Medical School, POB 607, FIN-33101 Tampere, Finland