Interleukin 4 deficiency limits the development of a lupus-like disease in mice triggered by phospholipids in a non-bilayer arrangement.

Non-bilayer phospholipids arrangements (NPAs) are transient molecular associations different from lipid bilayers. When they become stable, they can trigger a disease in mice resembling human lupus, which is mainly characterized by the production of anti-NPA IgG antibodies. NPAs are stabilized on liposomes or cell bilayers by the drugs procainamide or chlorpromazine, which produce drug-induced lupus in humans. Here, we evaluated the participation of the T 2 response, through its hallmark cytokine IL-4, on the development of the lupus-like disease in mice. Wild-type or IL-4 knockout BALB/c mice received liposomes bearing drug-induced NPAs, the drugs alone, or an anti-NPA monoclonal antibody (H308) to induce the lupus-like disease (the last two procedures stabilize NPAs on mice cells). IL-4 KO mice showed minor disease manifestations, compared to wild-type mice, with decreased production of anti-NPA IgG antibodies, no anti-cardiolipin, anti-histones and anticoagulant antibodies, and no kidney or skin lesions. In these mice, H308 was the only inducer of anti-NPA IgG antibodies. These findings indicate that IL-4 has a central role in the development of the murine lupus-like disease induced by NPA stabilization.