Sympathetic nervous system-immune interactions in autoimmune lymphoproliferative diseases

With some exceptions, the sympathetic nervous system has often been regarded as an immunosuppressive system. However, we know now that the immunoregulatory role of the sympathetic nervous system cannot be described in such absolute terms. Indeed, sympathetic neurotransmitters can inhibit or stimulate an immune response depending on numerous variables, which include the type of adrenergic receptor involved, the kind of antigen that triggers the immune response, and the subset of immune cells affected. A most important consideration is that immune and sympathetic responses are phasic phenomena and the step of the immune response at which lymphoid and/or accessory cells are exposed to neurotransmitters, or deprived from their presence, seems decisive for the outcome. The large amount of basic research on the role that the sympathetic nervous system plays in neuroimmunomodulation has prompted studies on its pathological implications. Systemic lupus erythematosus is an autoimmune lymphoproliferative disease that has mainly been associated with a Th2 shift and increased humoral responses. Lpr/lpr mice, which express a defective Fas, are commonly used as a model of this disease, and more recently, also of the autoimmune lymphoproliferative syndrome. We have found that, besides defects in the Fas pathway, lpr/lpr mice have an altered sympathetic innervation, and that this alteration contributes to the pathogenesis of the disease. The results strongly support the hypothesis that the sympathetic nervous system can modulate the expression of autoimmune lymphoproliferative diseases.