Rheumatoid arthritis (RA) is a chronic arthritic condition that can lead to
deformities and disabilities.
Interleukin-18 (IL-18) is a proinflammatory
cytokine known to play a role in the acute and chronic inflammatory phases of RA.
IL-18 binding protein is the natural antagonist of
IL-18 protein. We aim to identify the effect of
HLA-DRB1*04 gene polymorphisms on
IL-18 and IL-18BP gene expressions profiles as well as the time-course profiles following in vitro stimulation with
mitogens. Peripheral blood mononuclear cells from 16 RA patients and 21 healthy controls were cultured for 1, 4, 8, 12, 24, 48 and 72 h following stimulation with either LPS or PHA.
mRNA expression of
IL-18 and IL 18BP were determined by quantitative real-time PCR using a comparative Ct (threshold cycle) method.
IL-18 levels in supernatants were measured by
enzyme-linked
immunosorbent assay. Basal
mRNA (4.5-fold) and
protein levels of
IL-18 were increased and IL-18BP
mRNA expression was decreased (8-fold) in RA patients when compared to controls. Similarly, increased
IL-18 levels were observed in active RA patients, whereas IL-18BP expression was increased in inactive patients. There was an increase in
mRNA and
protein levels of
IL-18 in RA patients that peaked at 4 h and 8 h respectively following LPS stimulation. A similar profile was observed for IL-18BP; however, the expression level was higher in controls than RA patients. Persistent high production of
IL-18 in RA is associated with
disease progression and
IL-18 BP seems to inhibit this activity.