Interleukins (IL-23 and IL-27) serum levels: Relationships with gene polymorphisms and disease patterns in multiple sclerosis patients under treatment with interferon and glatiramer acetate.

BACKGROUND

interleukin 23 (IL-23) is an important factor involved in the survival and proliferation of T helper 17 cells (Th17), known for their implication in multiple sclerosis (MS). By contrast, IL-27 regulates and modulates the function of T lymphocytes, in particular as a suppressor of Th17 differentiation. The aims of the study were i) to test the association of cytokines with the clinical and genetic characteristics in each of the multiple sclerosis groups (CIS - clinically isolated syndrome, RRMS - relapsing-remitting MS and SPMS - Secondary progressive MS) and ii) to evaluate the association between serum levels of IL-23 and IL-27 with (IL-27), (IL-27) and (IL-23) gene polymorphisms in RRMS patients.

METHODS

Blood samples were obtained from 82 patients diagnosed with MS under treatment with glatiramer acetate (GA), interferon beta (IFN) 1 A and 1 B. IL-23 and IL-27 serum concentrations were measured by enzyme-linked immunosorbant assay (ELISA). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used in order to determine the genotypes for (IL-23) polymorphisms, (IL-27) and (IL-27).

RESULTS

Patients with SPMS, RRMS and CIS respectively differed significantly regarding age distribution (p = 0.003) but the studied MS groups were similar regarding age at disease onset (p = 0.528) and treatment type (p = 0.479). A significant increase of mean serum IL-27 was noticed in cases with early onset (age at disease onset <28 years) of RRMS (mean difference: 4.2 pg/ml, 95% CI: 0.8-5.3 pg/ml), compared to cases with later onset of RRMS (age at disease onset ≥28 years). RRMS patients with wild GG genotype of (IL-23) showed a significant increase of mean serum IL-23 than patients with variant AG genotype (mean difference: 115.1 pg/ml, 95% CI: 8.6-221.6 pg/ml). A trend for a higher increase in means of serum IL-23 (p = 0.086) was observed in RRMS patients carriers of AA genotype of (IL-27) polymorphism in comparison with patients with AG or GG genotypes. We found no significant monotonic correlation of IL-27, IL-23 serum levels with age at disease onset (years) and duration of disease (p > 0.05) in the CIS and SPMS group respectively but a significant correlation between IL-23 and the duration of disease-modifying treatment was noticed only in the SPMS group.

CONCLUSIONS

The results of the current study suggest an association between IL-23 levels and the gene polymorphism and also a relationship between IL-27 serum levels and early age at disease onset in RRMS patients.