Longitudinal analysis of serum interleukin-18 in patients with familial Mediterranean fever carrying MEFV mutations in exon 10

Background: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the MEFV gene. Mutations in exon 10 are associated with typical FMF phenotypes, and patients with exon 10 mutations have higher serum levels of interleukin (IL)-18 both during attacks and afebrile phases, compared to those without exon 10 mutations. However, longitudinal changes of serum IL-18 in FMF have not been fully characterized. Methods: We serially evaluated serum levels of pro-inflammatory cytokines, including IL-18, in 12 patients with FMF carrying exon 10 mutations, all of whom showed typical FMF attacks. Results: Markedly high concentrations of IL-18 were observed in all patients at diagnosis (5099 +/- 6084 pg/mL). Serum IL-18 levels declined progressively after colchicine treatment in 7 patients (group A), whereas 5 patients showed continued elevation of circulating IL-18, despite declines in IL-6 and neopterin (group B). The mean follow-up times in the two groups were 4.7 +/- 3.2 and 4.8 +/- 1.5 years, respectively. The mean serum IL-18 level at the last hospital visit in group B was 4190 +/- 2610 pg/mL. There were no differences in onset age, initial IL-18 levels, and colchicine doses between the groups. FMF attacks almost disappeared in both groups, but there were trends towards more frequent subtle symptoms such as abdominal discomfort in group B. Conclusions: Sustained elevation of serum IL-18 may suggest the presence of persistent subclinical inflammation. Therefore, longitudinal examination of serum IL-18 may contribute to better follow-up of FMF patients with exon 10 mutations.