MFP14, a multifunctional emerging protein with immunomodulatory properties, prevents spontaneous and recurrent autoimmune diabetes in NOD mice

Aims/hypothesis. To test the effects of multifunctional protein 14 (MFP14), which shares structural homology with heat shock proteins (HSPs), on the d evelopment of Type I; (insulin-dependent) diabetes mellitus in NOD mice. Methods. MFP14 was given to euglycaemic female NOD mice from either the 4(t h) to the 25(th) or from the 12(th) until the 35(th) week, or commencing on e day before islet transplantation and until the reappearance of hyperglyca emia. Pancreata from NOD mice treated with multifunctional protein 14 for 1 4 consecutive weeks until 18 weeks of age were examined histologically for insulitis. Anti-CD3 and/or lipopolysaccharide (LPS)-induced blood levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-10, IL-12 and tumour necros is factor (TNF)-alpha were measured by ELISA in 10 week-old female NOD mice treated for 6 consecutive weeks with either MFP14 or PBS. Unless otherwise stated, multifunctional protein 14 was administered daily 5 times a week a t a dose of 25 mug. Control mice received PBS or, in selected experiments, heat-inactivated MFP14. Results. MFP 14 treated mice had a significantly lower incidence of spontan eous diabetes compared to control mice. The MFP14 was equally effective bot h upon early and late prophylaxis and the protection persisted until week 5 0 in mice treated from weeks 4 to 25. Insulitis was significantly reduced b y the MFP14. The MFP14 also delayed recurrence of hy perglycaemia in syngen eic islet-transplanted NOD mice. Although MFP14 reduced anti-CD3 and/or LPS -induced blood levels of IFN-gamma, TNF-alpha and IL-12 it increased IL-4 a nd IL-10. Conclusion/interpretation. The MFP14 could be a possible candidate for the prevention or early treatment of human Type I (insulin-dependent) diabetes mellitus.