IFN[gamma], IL4, TNF[alpha], and TNF[beta] responses to EBNA1 and IL18, IL4, and IL6 responses to EBV-EA/D correlated negatively with sSLEDAI scores of SLE patients, respectively.
As IL1[beta], TNF[alpha], IL18, and GM-CSF secretion was induced to a normal level upon EBNA1 stimulation in SLE patients, the macrophages of SLE patients are assumedly functional and responsive to the latent EBV infection.
Caption: Figure 3: Cytokines involved in various T-cell responses, IL18 (a), IL10 (b), and IL4 (c), with similar induction in SLE patients and in HCs upon EBNA1 stimulation.
Caption: Figure 6: Cytokines, IL12 (a), IL18 (b), IL10 (c), and TNF[alpha] (d), with similar induction in SLE patients and in HCs upon EBV-EA/D stimulation.
The principal explanatory variables were the 5 genotyped IL18 polymorphisms and inferred haplotypes.
4860 A>C was the only exonic SNP found within IL18 by IIPGA; however, it is nonsynonymous-no other potentially functional SNPs were found.
The 5 IL18 polymorphisms generated 4 common haplotypes (frequency >10%) accounting for 93% of the inferred haplotypes for both cohorts.
When this hypothesis was tested in CUDAS and CUPID, none of the IL18 haplotypes were associated with risk of carotid plaque or mean IMT (data not shown).
The data presented here demonstrate that genetic variation within the IL18 gene affects IL-18 protein concentrations and may therefore affect IL-18 concentrations at the site of disease.
10) highlighted the role of the IL18 gene in cardiovascular disease, demonstrating that IL18 haplotypes caused variation in IL-18 serum concentrations and were associated with cardiovascular mortality.
The lack of any strong association between IL18 genetic variation and presence of carotid plaque or carotid IMT, despite IL-18 concentrations being associated with carotid IMT in previous studies (37) but not those studied here (34), is suggestive of several explanations.
In conclusion, we show that common genetic variation within IL18 is associated with interindividual differences in concentrations of IL-18 protein.