Development of systemic lupus erythematosus in mice is associated with alteration of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs Luisa Bracci-Laudiero a,b, *, Luigi Aloe b , Carina Stenfors a , Elvar Theodorsson c , Thomas Lundeberg a a Karolinska Institutet, Stockholm, Sweden b Institute of Neurobiology CNR, Rome, Italy c University Hospital, Linkoping, Sweden Received 27 February 1998; received in revised form 14 April 1998; accepted 14 April 1998 Abstract In the present study we used a well-characterised model of murine lupus, the female NZB/W hybrid, to study the possible involvement of neuropeptides in the pathogenesis of systemic lupus erythematosus (SLE). Analysis of neuropeptides with a possible role in inflammation showed that substance P (SP) calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) are present in increased quantities in the inflamed kidneys of SLE mice, confirming their involvement in local inflammation, while there is a general reduction in the peptide concentrations in the lymphoid organs of lupus mice, except for NPY. Our results suggest that the altered neuropeptide concentrations observed in the SLE lymphoid organs may be partly responsible for the altered immune response and contribute to the development of autoimmune diseases.  1998 Elsevier Science Ireland Ltd. All rights reserved Keywords: Neuropeptides; Neuropeptide Y; Substance P; Calcitonin gene-related peptide; Inflammation; Systemic lupus erythematosus; Nerve growth factor Systemic lupus erythematosus (SLE) is a multi-systemic disease of unknown aetiology, characterised by altered humoral and cellular immune response. The production of pathological autoantibodies and the deposition of immune complexes affect different tissues and organs: skin lesions, nephritis, vasculitis, arthritis, haematological abnormalities, neurological and mental dysfunction are all clinical mani- festations of the disease. However, although the diagnosis can be established with certainty, no effective treatment for SLE is yet available. We have recently shown that SLE patients [6] and lupus NZB/W mice [4] present increased levels of serum nerve growth factor (NGF) and that NGF production is correlated with the inflammatory activity of the disease [4,6]. NGF accumulates at the sites of inflam- mation and has been shown to regulate the synthesis of sensory peptides during prolonged inflammatory processes in vivo [10]. We recently showed that NGF, actively pro- duced by B-cells [21], can induce NPY production in T- lymphocytes [5]. This sharing of common signal pro- teins suggests a close interaction between the nervous and immune systems. The structural link between the two systems exists through the innervation of the immune organs. Noradrener- gic and peptidergic fibres [16] are distributed within the parenchyma of both primary and secondary immune organs. The nervous system is thus able to transmit signals to and communicate directly with the immune system. Surgical denervation and chemical sympathectomy can alter cellular proliferation, B- and T-cell responsiveness and lymphocyte migration in lymphoid organs [17]. In vitro studies have shown that neuropeptides can have numerous effects, either inhibiting or stimulating the proliferation, differentiation and functions of immune cells [19]. Taken together, these findings indicate that the immune response can be regulated Neuroscience Letters 248 (1998) 97–100 0304-3940/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00342-5 * Corresponding author. Institute of Neurobiology, CNR, Viale Marx 13, 00137 Rome, Italy. Tel: +39 6 86090288; fax: +39 6 86090370; e-mail: luisa@biocell.irmkant.rm.cnr.it