Objective Systemic lupus erythematosus (SLE) is a systemic chronic autoimmune disease characterized by dysregulation of immune system. Increased immune cell activity, impaired phagocytosis as well as formation and deposition of autoantibodies and immune complexes result in damage to various organs. Glucocorticoids, antimalarial drugs and immunosuppressive agents are part of the current treatments, but large numbers of SLE patients do not responds well to these treatments or have severe side effects. This necessitates the development of new therapeutic options.

The macrocyclic lactone Oxacyclododecindione (Oxa) is described as a good therapeutic option in a SLE-model. However, Oxa is difficult to produce, so derivatives could be an alternative. The Oxa-derivative 14-Deoxy-14-methyloxa (14D14m) shows the same anti-inflammatory effects as Oxa in a murine in vitro model, so we tested this derivative in the SLE-model as well.

Methods We tested 14D14m as a treatment in MRL-Fas^lpr mice, a model for SLE. The mice were treated every other day for three weeks after the onset of first visual symptoms (lymph node swelling and skin lessens). The effect of 14D14m were also tested in vitro on the human monocyte and macrophage cell line MM6 as well on primary PBMC from SLE patients and healthy controls under inflammatory conditions. Effects of 14D14m validated with histopathological examination, immunostainings and qPCR.

Results In MRL-Fas^lpr mice the treatment with 14D14m reduced significant the lymph node swelling and the splenomegaly. We also see an altered immune cell composition with fewer monocytes/macrophages, Th1- and Th2-cells in the lymph nodes and less CD68⁺-cells in the kidney of treated mice. In vitro 14D14m significantly reduced the induced mRNA expression of inflammatory genes in the MM6 cell line as well in the PBMC from SLE patients and healthy controls.

Conclusions Results to date demonstrate a therapeutic effect of 14D14m on the disease development of SLE-mice, with a significant reduction of lymph node swelling and splenomegaly. In addition, the first result in human immune cells show a good anti-inflammatory effect of 14D14m and give the first indication of efficacy in human cells. However, further studies needed to evaluate whether 14D14m is a new therapeutic approach of SLE.