IL-4 role in the development of the lupus mouse model induced by non-bilayer phospholipids arrangements

Abstract

Abstract Non-bilayer phospholipids arrangements (NPAs) are lipid molecular associations that are different from the bilayer and are transient. However, if they become stable, they can trigger a disease in mice that is similar to human systemic lupus erythematosus. NPAs can be stabilized in liposomes formed by cylindrical and conical lipids or in cell membranes by drugs such as procainamide or chlorpromazine. In wild-type BALB/c mice, this lupus model has been developed by administering liposomes with NPAs induced and stabilized with procainamide or chlorpromazine, by administering the drugs alone or by administering the monoclonal antibody H308; these last two procedures stabilize the NPAs in the membranes of mouse cells. Anti-NPAs, anti-cardiolipin, anti-histones and anti-coagulants auto-antibodies have been detected in the serum of these mice; in addition, the mice present facial lesions and alterations in the skin and kidney. In this work, we evaluated the participation of the T H2 response, through IL-4, which is its most characteristic cytokine, in the development of the NPAs-induced lupus model in mice. Wild type or IL-4 knockout BALB/c mice were administered with liposomes bearing drug-induced NPAs, the drugs alone, or anti-NPA H308 antibody to induce the lupus-like disease. 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 suggest that IL-4 has a key role in the development of the murine lupus-like disease induced by NPA stabilization. This study was supported by grants from IPN (SIP20232128, SIP20232132 and SIP20232135).