The plasmid backbone and multiple immune-regulating potentials of IL-18 appeared to play the major role in the pIL-18 coadministration with rIL-4-mediated immunomodulation of arthritis, resulting in inhibition of Th17 and Th1 inflammatory immune responses and improving anti-inflammatory mediators by a GATA-3-dependent mechanism. Here, GATA3 is linked to arthritic joint disease.