Neuroendocrine immunomodulation

Close interaction between the immune and nervous systems is well documented. The ability of immunocompetent cells to express receptors to neuroendocrine mediators as well as secrete many of them is proved. The current literature suggests that the hormones of the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonodal axes play the most significant role in the regulation of immune responsiveness. On the other hand, the immune system communicates with the CNS directly through the cytokines that are able to cross the blood-brain barrier, or directly via the nervus vagus, as well as via secondary messengers. Receptors to a number of cytokines have been found in the nervous tissue. Moreover, glial cells are able to secrete cytokines in the amount significant enough for at least autocrine action. In this article, the authors review the role of the "major" stress hormones such as cortisol, DHEA, growth hormone in the regulation of immune response, as well as neuro- and psychotropic properties of two major groups of cytokines that support cell-mediated (Type 1) and humoral (Type 2) immune reactions. This review emphasizes neuro-endocrine-immune interactions in response to infection both under laboratory and clinical conditions.     

Mechanisms of conditioned immunomodulation

This article presents some recent work from our laboratory indicating that multiple physiological systems play a role in conditioned immunomodulation. The first study shows that naltrexone, but not N-methylnaltrexone, blocks the suppressive effects of an aversive conditioned stimulus on Con-A-induced proliferation and natural killer cell activity of splenic lymphocytes. This finding indicates that central opioid activity is involved in the conditioned effects. The second study shows that the β-adrenergic antagonists atenolol and ICl-118,551 block the suppressive effects of an aversive conditioned stimulus on Con-A-induced proliferation, but have no effect on natural killer cell activity. This result indicates the involvement of the adrenergic system in a subset of the conditioned effects. Collectively, these experiments provide evidence that both the opioid system and the sympathetic nervous system are involved in conditioned immunomodulatory changes elicited by an aversive conditioned stimulus.     

Fat chance of immunomodulation

Lipids consumed in the diet, including fatty acids, cholesterol and fat-soluble vitamins, exert effects upon the immune system. This might suggest a nutritionally based therapeutic route for diseases characterized by inappropriate immune responses. A recent meeting¹ reviewed the current state of this field.     

Styrene-induced immunomodulation in mice

Male mice given different oral doses (0.05, 0.03 or 0.02 x LD50/animal/day) of styrene (LD50 = 1 g/kg) daily for 5 days did not incite any overt toxicity in lymphoid organs or on hematologic parameters. At the tested dose levels styrene produced a mild reduction in the organ weight of adrenal and spleen and slight reduction in the cellular viability of lymph nodes. There was a dose-dependent suppression in the humoral immune response (IgM-producing PFCs of spleen and serum anti-SRBC HA titre) to SRBC. The proliferative response to the B-cell mitogen, LPS however revealed a significant increase in the incorporation of 3HT with middle and lowest doses of styrene. The results of cell-mediated immunity appeared somewhat unexpected and more complex as exposure resulted in a dose-dependent enhancement in the cutaneous DTH reaction to SRBC together with increased blastogenic response of splenic lymphocytes to phytohaemagglutinin (PHA). Additionally, there was significant impairment in the functional activity (NBT reduction, attachment and phagocytic indices) of nonadherent and adherent peritoneal exudate cells. Based on the present data the study identifies the immunotoxic potential of styrene and which acts differently on various arms of the rodent's immune system.     

Mechanisms of immunomodulation by drugs

Immunomodulators are those extrinsic or intrinsic substances which regulate or alter the scope, type, duration or competency of the immune response. This paper presents an overview of the mechanisms of immunomodulation, and discusses selected chemical and biologic substances which are capable of modifying the immune or biologic response of the organism. The immunopharmacology, including in vivo and in vitro assays, of a novel acridine immunomodulator is discussed. This low molecular weight compound is an immunomodulator and anti-cancer adjuvant, which has been shown to induce high levels of circulating interferon in mice, protect mice against lethal viral infection, stimulate macrophage and NK cell cytotoxicity for tumor cells, partially restore humoral and cellular immune responses in tumor bearing immunosuppressed mice, and augment the cytotoxic T-lymphocyte response to syngeneic tumor cells. Tissue changes, consisting of presence of drug bound to lysosomal membranes, perivascular infiltrates in mouse liver, glomerular hyalinization in mouse kidney, and focal myocardial changes in mice are described. The compound persists intracellularly for extended periods of time in cells with high lysosomal activity. The tissue changes are interpreted to be a result of overloading of cellular mechanisms for elimination from the cells involved.     

Immunological principles regulating immunomodulation with biomaterials

The immune system has evolved to recognize and eliminate pathogens; this recognition relies on the identification of structural molecular patterns within unique tissue microenvironments. Therefore, bioengineers can harness these immunological cues to design materials that modulate innate and adaptive immunity in a controlled manner. This review acts as an immunology primer by focusing on the basic molecular and cellular immunology principles governing immunomodulation with biomaterials.     

Antigen-specific immunomodulation via altered peptide ligands

An important subgroup of human cellular receptors uses peptides as signaling molecules. Modifications of these signaling peptides, usually by amino acid substitutions in crucial receptor contact sites (i.e., altered peptide ligands, APLs), is an approach for highly selective and specific modulation of the receptor function. One of the major applications of APLs is immunology, where APLs have been examined for therapeutic modulation of T cell function, both for diseases characterized by unwanted activation of T cells (e.g., autoimmune diseases) and for disorders with suboptimal T cell activation (e.g., immunotherapy of cancers and infectious disorders). APLs also occur in vivo, for example, as escape mutants of infectious agents, and play an important role in thymic positive selection. We summarize current knowledge of the basic mechanisms of the effects of APLs with special focus on T cell receptor signaling and the use of APLs for the treatment of autoimmune diseases.     

Immunology and immunomodulation of corneal transplantation

Corneal allografts are the oldest, most common, and most successful transplants performed on humans and animals. The cornea is endowed with a constellation of unique factors that contribute to its immune privilege and the low incidence of immune rejection. In spite of this immune privilege, 10 percent of first-time corneal grafts will undergo immune rejection. Several novel therapeutic strategies hold promise for modulating the alloimmune response by either promoting antigen-specific tolerance or redirecting the host's response from a Th1 pathway toward a Th2 pathway.     

Conditional immunomodulation following training with cyclophosphamide

In 5 experiments, paired-group rats received a conditional stimulus (CS) paired with the immunosuppressive drug cyclophosphamide (CY). In Experiments 1-3, the CS was saccharin (SAC). Consistent with previous reports, these rats acquired a SAC aversion. However, there was no evidence of conditional immunosuppression. Rather, when reexposed to SAC in conjunction with an antigenic challenge, paired-group rats evidenced hemagglutination antibody titers similar to those seen in rats that never received the immunosuppressant. That is, the usual effect of CY in compromising immunological functioning was attenuated or eliminated by the CY-paired flavor. The findings of Experiments 1-3 were confirmed in Experiments 4-5, which used nongustatory CSs. Both audiovisual (noise and flashing-light) and pharmacological (pentobarbital) cues were also effective signals for CY injection. Following pairing with CY, these cues protected animals from the immunosuppressive effects of the drug.     

Thymulin and its role in immunomodulation.

Even though thymulin was isolated, sequenced and characterised some 20 years ago and later identified as a thymic hormone involved in immunomodulation, much more work is still required to further understanding of the mechanisms of action(s) of this peptide. Since the observation, by a semiquantitative bioassay, of diminished levels of thymulin in immunodeficiency and autoimmune disease, new data obtained by radioimmunoassay have not only confirmed previous observations but also demonstrated that thymulin plays a role in the interaction between the immune system and the neuro-endocrine system. In this paper we give an up to date account of recent developments in research into the role of thymulin in immunomodulation.     

Positive and negative immunomodulation by opioid peptides

The data that follow review part of the existing evidence concerning the neuroimmune functions mediated by opioid peptides, with particular regard to dual immunomodulatory effects. Limited references to substances other than opioid peptides are included, mainly to emphasize the possible similarities in the mediation of neuroimmune interactions by different informational substances, while the interactions directed from the immune to the nervous system have deliberately been omitted.     

间充质干细胞在炎症免疫调节中的作用及应用进展

背景：研究表明,间充质干细胞的主要功能有直接参与损伤修复,分泌生长因子,调节免疫和炎症,抗氧化应激等,可用于治疗多种急、慢性疾病。 目的：综述间充质干细胞在炎症免疫调节中的研究进展。 方法：以“干细胞,间充质干细胞,免疫调节,炎症,免疫细胞,炎症因子,治疗”为中文检索词,以“stem cells,mesenchymal stem cells,immune regulation,inflammation,immune cells,inflammatory factors,treatment”为英文检索词,在万方、中国知网期刊全文数据库和PubMed数据库检索2005年1月至2015年8月有关干细胞参与炎症免疫调节的文献。排除陈旧性和重复性研究,最终纳入40篇文献进行综述。 结果与结论：间充质干细胞因其具有免疫调节及多向分化的特性,越来越受到临床的重视,同时间充质干细胞易于从不同组织中获取并且具有良好的体外扩增能力,使得其在组织损伤炎症与修复的临床运用中具有广阔的前景。作为最有希望进入临床应用阶段的种子细胞,间充质干细胞在许多疾病的治疗中表现出了它的优越性,特别是对于免疫调节失衡导致的炎症性相关疾病的治疗中表现出良好的效果。相信在未来的细胞生物治疗领域,间充质干细胞将占有重要的地位。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程