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      Strain Differences in the Expression of Corticotropin-Releasing Hormone Immunoreactivity in Nerves That Supply the Spleen and Thymus

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          Abstract

          The existence of nerve fibers containing corticotropin-releasing hormone (CRH) immunoreactivity in primary and secondary lymphoid organs from three strains of young adult male rats was examined. Spleens and thymuses from Fischer 344 (F344), Sprague-Dawley (SD) and Lewis (LEW) rats were prepared for immunocytochemistry using antisera directed against CRH. In F344 and SD rats, we were unable to demonstrate CRH-immunoreactive nerves in either the thymus or the spleen. Despite the lack of CRH-containing nerves, CRH immunoreactivity was present in pleotropic cells in the septum, cortex and medulla of the thymus, and in the red and white pulp of spleens from F344 and SD rats. In contrast, CRH+ nerves were found in thymuses and spleens from LEW rats. CRH+ nerves coursed in the interlobular septa, capsule, cortex and medulla of the LEW rat thymus. Large CRH-immunoreactive nerve bundles were present in the hilar region of the LEW rat spleen, and individual CRH+ fibers coursed in the capsule, trabeculae, red pulp, venous sinuses and marginal zone of the white pulp of the spleen. These findings indicate strain differences in neurotransmitter-specific nerves that innervate the rat spleen and thymus under basal conditions.

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          Most cited references 17

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          Corticotropin releasing hormone related behavioral and neuroendocrine responses to stress in Lewis and Fischer rats.

          We have recently shown that susceptibility to streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats is related to a lack of glucocorticoid restraint of inflammation while the relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats is related to their greater hypothalamic-pituitary-adrenal (HPA) axis response. The difference in pituitary-adrenal responsiveness results from decreased inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion in LEW/N rats. Because CRH not only activates the pituitary-adrenal axis, but also is associated with behavioral responses that are adaptive during stressful situations, we wished to determine if the differential LEW/N and F344/N CRH responsiveness to inflammatory mediators could also be associated with differences in neuroendocrine and behavioral responses to physical and emotional stressors. In this study, LEW/N rats exhibited significant differences compared to F344/N rats, in plasma adrenocorticotropin hormone (ACTH) and corticosterone responses during exposure to an open field, swim stress, restraint or ether. Furthermore, hypothalamic paraventricular CRH mRNA expression was also significantly lower in LEW/N compared to F344/N rats after restraint. These differences in neuroendocrine responses were associated with differences in behavioral responses in LEW/N compared to F344/N rats in the open field. Outbred HSD rats, which have intermediate and overlapping arthritis susceptibility compared to LEW/N and F344/N rats, exhibited intermediate and overlapping plasma corticosterone and behavioral responses to stressful stimuli compared to the two inbred strains. These data suggest that the differences in CRH responses in these strains may contribute to the behavioral and neuroendocrine differences we have observed. Therefore these strains may provide a useful animal model for studying the relationship between behavior, neuroendocrine and inflammatory responses.
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            Stimulatory effect of corticotropin-releasing neurohormone on human lymphocyte proliferation and interleukin-2 receptor expression.

            The supplementation of corticotropin-releasing factor (CRF) into the cultures of human blood lymphocytes caused increased proliferation both in the absence and presence of T cell mitogens such as concanavalin A and phytohemagglutinin. The stimulation of concanavalin A response was much higher with CRF ligand as compared to Tyr-CRF, CRF-antagonist and sauvagine, and this response was blocked by CRF-antagonist. The lymphocyte proliferative response to stimulation by pokeweed mitogen or monoclonal antibody to CD3 antigen (OKT3) and the activity of natural killer (NK) cells was not affected by CRF. However, this neuroendocrine hormone, in addition to its ability to stimulate lymphocyte proliferation, enhanced expression of interleukin-2 receptors (IL-2R) on T cells (activated T cells) as revealed by a 2-fold increase in the proportion of IL-2R+T cells after the culture of lymphocytes for 3-5 days in the presence of CRF. Based on these findings, we suggest that CRF plays an important role in the modulation of the neuroendocrine-immune circuity.
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              Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation?

               T. Fink,  E. Weihe (1988)
              By the use of light microscopic (LM) immunohistochemistry, the presence of peptides and of dopamine beta-hydroxylase (DBH) in nerves supplying mammalian (guinea pig, rat, cat, pig, mouse, human) lymph nodes were examined. In all species, lymph nodes of various somatic and visceral regions were found to contain nerve fibers which stained for neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), calcitonin gene-related peptide (CGRP) or DBH. SP- and CGRP-immunoreactive (ir) fibers completely overlapped and exhibited the widest distribution. They were present in perivascular, paravascular and many non-vascular fibers travelling in close contact with lymphoid cells. In contrast, NPY-ir fibers coincided with those staining for DBH, prevailed in perivascular plexus and only rarely branched off into lymphoid parenchyma. Alternate staining of adjacent sections revealed that SP/CGRP-ir fibers were different from NPY/DBH-ir fibers. The distribution of VIP-ir fibers was identical to that of PHI-ir fibers and partially overlapped with that of ir-NPY/DBH or ir-SP/CGRP fibers. We conclude that the NPY innervation of lymph nodes is sympathetic noradrenergic while nerves coding for co-existing SP and CGRP are most likely of sensory origin. The nerves containing co-existing VIP and PHI may be of heterogenous origin (sensory, cholinergic sympathetic, and/or parasympathetic). We suggest that these distinct sensory and autonomic peptidergic pathways linking the nervous system with the lymph nodes may play a differential role in bidirectional neuroimmunomodulation.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2001
                September 2001
                14 September 2001
                : 9
                : 2
                : 78-87
                Affiliations
                aCenter for Neuroimmunology, Loma Linda University School of Medicine, Loma Linda, Calif., bEmergency Department, University of Rochester, N.Y., and cHoover Arthritis Research Center, Sun Health Research Institute, SunCity,Ariz.,USA
                Article
                49010 Neuroimmunomodulation 2001;9:78–87
                10.1159/000049010
                11549889
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 17, References: 59, Pages: 10
                Categories
                Original Paper

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