Neuropeptide Y: a modulator of apoptosis in systemic lupus erythematosus

ABSTRACT

Systemic lupus erythematosus [SLE] is a multisystem disease characterized by the production of pathological autoantibodies and altered humoral and cellular immune responses. The death receptor Fas is known to induce apoptosis upon interaction with its ligand with consequent activation of caspases and is reported to have an important role in the pathogenesis of SLE. Recently, it has been reported that the nervous system interacts with and directly modulates the immune response through the production of certain neuropeptides as neuropeptide Y [NPY]. To assess the serum level of NPY in SLE patients and to investigate its correlation with the activity of the disease, the level of Fas expression on mononuclear cells and the incidence of apoptosis in SLE patients. The study was conducted on 20 SLE patients and 10 healthy controls. Fas expression was assessed with flow cytometry using mouse antihuman FITC conjugated anti-CD95. The% of apoptotic cells was assessed after cell culture with flow cytometry using propidium iodide staining. NPY was assessed with competitive radioimmunoassay kit for both patients and controls. Both Fas and NPY levels were found to be significantly elevated in SLE as compared with healthy controls [p< 0.01]. Moreover, both levels were found to correlate significantly with the activity score of the disease and with each other. However, despite the elevated Fas expression, the% of apoptotic cells are not significantly increased in SLE compared to healthy controls. Fas expression could be considered a marker of lymphocyte activation in SLE. The presence of high levels of neuropeptides as NPY reflects the link between nervous and immune system. NPY could play an important role as endogenous modulator of the immune response in SLE probably through their inhibiting effect on Fas ligand expression and so switch the lymphocytes to an apoptosis resistant phenotype, which could lead to the activation of autoreactive cells. Thus neuropeptide Y may play an important role in the pathogenesis of SLE