Evaluation of the circulating levels of IL-33 in patients with osteoarthritis: role of rs1929992 variants.

BACKGROUND

Osteoarthritis (OA) is among the common chronic health conditions which impacts many aspects of an individual's life from physical function to mental health. Inflammation, in the joint as well as system inflammation is among the many mechanisms hypothesized to be involved in OA. IL-33 which belongs to the IL-1 family, is considered as an alarmin in OA. IL-33 binds to a group of receptors to stimulate signaling among which is the ST2L receptor that induced the activation of NFƙb, thus, working as a booster of the inflammatory cascade. Many polymorphisms have been identified on the IL-33 gene which are assumed to be associated with inflammatory diseases.

METHODS

In the current double-blind placebo-controlled clinical trial study, patients diagnosed with knee OA were randomly divided into two groups: one group received metformin and the other received a placebo for 16 consecutive weeks (starting at 0.5 g/day, increasing to 1 g/day at week two, and increasing to 1.5 g/day for the remaining 14 weeks). Besides the evaluation of the clinical response to metformin using the Knee Injury and OA Outcome Score (KOOS) questionnaire, the serum levels of IL-33 was measured using enzyme-linked immunosorbent assay (ELISA) kits before (time 0) and after treatment (month 4). Genetic polymorphism of rs1929992 was assessed using in extracted DNAs using PCR-RFLP method.

RESULTS

Serum levels of IL-33 were significantly higher in OA patients compered to healthy individuals (P<0.001). Mutant allele (G allele) of the rs1929992 was significantly associated with OA (P=0.028; OR=1.9; 95%CI: 1.02-3.6). AG+GG genotypes were also associated with OA (P=0.004; OR=3.8, 95%CI: 1.5-9.5). Metformin did not affect IL-33 levels (P>0.05). Variants of rs1929992 were not associated with response to metformin (P>0.05).

CONCLUSION

Our findings support the role of polymorphisms of IL-33 gene and circulating levels of IL-33 in OA. Drugs targeting IL-33 signaling pathway may propose beneficial effects in OA.