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Department of Medicine, Faculty of Medical and Human Sciences, Department of Endocrinology, Department of Medicine, Brigham and Women's Hospital, Thorn Bldg, 1405, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
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Kronenberg M 1993 Regional specialization of the mucosal immune system. Intraepithelial lymphocytes of the large intestine have a different phenotype and function than those of the small intestine . Journal of Immunology 151 1765 – 1776 . Cancello
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& Bowers 2010 ). Neuroendocrine and immune systems interact in a directional fashion. In this way, the status of pathogen recognition is communicated to the brain and the immune response is influenced by physiological changes. This explicit communication
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Department of Organismal Animal Physiology, The Clayton Foundation Laboratories for Peptide Biology, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525AJ Nijmegen, The Netherlands
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/signal transducer and activator of transcription (JAK/STAT) pathway, ultimately leading to changes in gene expression. Since its discovery as a regulator of interferon (IFN) responses in the immune system ( Schindler et al . 1992 , Darnell et al . 1994 ), JAK
Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, AV. Combatients de Malvinas 3105, 1427 Buenos Aires, Argentina
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Introduction Homeostatic regulation of immunity involves factors that are traditionally considered outside the immune system, including hormones and neurotransmitters. Thyroid hormones play critical roles in differentiation
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Introduction
Many publications in recent years have greatly enhanced our understanding of the interrelationship between the immune system and the hypothalamo-pituitary-adrenal axis (HPA). Previously, the primary interaction between the two systems was ascribed to the effects of glucocorticoids on the immune response (Fauci, 1979). Recent studies, however, have shown the presence of additional interactions between the immune system and the HPA axis, which have led some authors to postulate the existence of reciprocal circuits as summarized in Fig. 1. At this time several of the links are hypothetical, as many reports are contradictory, and await further research for confirmation. This review is an attempt to clarify this complex area and is a critical assessment of published data which has enabled such a diagram to be constructed.
For Fig.1 to be an accurate reflection of the physiological state, three major criteria have to be proven. These are (1) the presence of both
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Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.
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ABSTRACT
Opioid peptides have been shown to modulate various parameters of both the humoral and cellular arms of the immune system. The modulatory capacity of the peptides can often be substantially reduced in the presence of naloxone, an opioid receptor antagonist, indicating a classical ligand-receptor interaction. In order to characterize these interactions further, we investigated the characteristics of opioid receptors on a macrophage cell line, P388d1. A δ-class opioid receptor was found with an M r of 58 000. We also identified opioid receptors on MOLT-4 (T-cell) and IM-9 (B cell) cell lines as well as thymocytes and T celland B cell-enriched populations. Using the central (brain) κ-selective agonist, U-69,593, it was also determined that P388d1 cells possess κ-like opioid receptors. Scatchard analysis of the binding of [3H]U-69,593 revealed a single population of sites with a dissociation constant of 17 ± 3 (s.e.m.) nmol/l and a total number of binding sites of 53·8 ± 1·0 (s.e.m.) fmol/106 cells. Moreover, the racemic κ-selective agonist U-50,488H was able to displace 50% of [3H]U-69,593 binding at 8·0 nmol/l, whereas other opioid ligands such as [Met]-enkephalinamide (δ-selective) and [d-Ala2,N - Me - Phe4,Gly5 - ol] - enkephalin (μ - selective) were ineffective displacers of [3H]U-69,593 except at high concentrations.
Journal of Endocrinology (1989) 122, 161–168
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Recent studies have shown that the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), can affect both tissues and cells that are not directly involved in calcium homeostasis. In particular, a role for calcitriol as a regulator of immune cell differentiation and proliferation has been proposed. Specific high-affinity intracellular receptors for calcitriol (VDR) are detectable in activated T cells, and activated macrophages are able to synthesize calcitriol. A possible paracrine mechanism of action has been postulated. Vitamin D may therefore have a similar role to that of other immune regulatory molecules such as cytokines. The precise interaction of calcitriol with the cytokine network is not yet fully defined, but its ability to modulate immune cells in vitro and its association with inflammatory diseases are now well documented. These findings are outlined in this review with particular reference to effects on macrophages and lymphocytes.
Ectopic production of calcitriol
Initial evidence
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and function of immune cell populations that are required for endometrial repair and remodelling. Introduction Androgens play important roles in human health, including the development and maintenance of the reproductive system, regulating
