Review Involvement of pro-enkephalin-derived peptides in immunity M. Salzet * , A. Tasiemski Laboratoire d'Endocrinologie des Anne Âlides, UPRESA CNRS 8017, SN3, Universite  des Sciences et Technologies de Lille, 59650 Villeneuve d'Ascq Cedex, France Received 23 May 2000; received in revised form 2 August 2000; accepted 7 August 2000 Abstract It is widely accepted that all organisms have processes that maintain their state of health. Failure of these processes, such as those involving the naturally occurring antibacterial peptides, may lead to pathological events. Recent results demonstrate that these peptides, such as peptide B, appear in invertebrates and vertebrates (including humans) immediately after tissue trauma, and maintain themselves for long durations (over 4 h). Their degradation products lead to other in¯ammatory peptides, such as Met-enkephalin-Arg-Phe. These newly described antibacterial peptides, which are released and not induced, are present on neuropeptide precursors such as proenkephalin. This is a new ®eld of research, in that the same protein contains proposed neuropeptides, antibacterial peptides, and immune stimulatory peptides. The focus of this review is to describe how the pro- enkephalin derived peptides participate in immune processes. q 2001 Elsevier Science Ltd. All rights reserved. Keywords: Immunity; Opioids; Proenkephalin; Invertebrate; Neuroimmunity; Biosynthesis; Mammals Contents 1. Introduction .................................................................. 177 2. Pro-enkephalin-a-derived peptides in immunity ......................................... 178 2.1. Methionine-enkephalin is a pro-in¯ammatory messenger ............................. 178 2.2. Innate immune response mediated by pro-enkephalin-a-derived peptides .................. 181 2.3. Clinical evidence .......................................................... 183 3. Conclusion ................................................................... 183 Acknowledgements ................................................................ 184 References ...................................................................... 184 1. Introduction Secretory granules from adrenal medullary chromaf®n cells contain a complex mixture of low molecular mass constituents, such as catecholamines, ascorbate, nucleotides, calcium and several water- soluble peptides and proteins [1]. These components are released into the circulation in response to the splanchnic nerve stimulation [1]. Relatively large amounts of pro-enkephalin-A and chromogranin- derived peptides are also found [1]. Metz-Boutigue's team has shown in cattle that antibacterial activity is present within the intragranular chromaf®n granule matrix and the extracellular medium following Developmental and Comparative Immunology 25 (2001) 177±185 0145-305X/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0145-305X(00)00047-1 www.elsevier.com/locate/devcompimm * Corresponding author. Tel.: 133-3-2043-6839; fax: 133-3- 2004-1130. E-mail address: michel.salzet@univ-lille1.fr (M. Salzet).