Immune function

The class II cytokine receptor family includes receptors for interferon a/P (lEN a/P) and y (lENy) and IL-10. lEN-y immunoreactivity has been found in neurons in the hypothalamus, cerebral cortex, mammilary nuclei, and dorsal tegmentum. Astrocytes and microglia in vitro can be stimulated to express class II histocompatibiHty complex (MHC-II) antigens by lEN-y, which may be involved in the presentation of antigen to T-ceUs by astrocytes. Thus lEN-y may be critical in CNS-immune function and dysfunction especially in regard to neuronal and gHal apoptotic processes. 

One component of the age-ielated decline in immune function is decreased production of the lymphokine that promotes the growth of T-ceUs, interleukin 2 (IL-2). Administration of recombinant-derived IL-2, both in vitro and in vivo, appears to restore certain immune functions in aged mice. Recovery of T-regulatory effects on B-ceU differentiation has been reported in human cells from elderly patients treated with IL-1 and/or IL-2 (42). Similar effects have been observed in the presence of the pentapeptide thymopentin [69558-55-0] (Arg Lys Asp Val Tyr), a weU-known IL-2 inducer. Recombinant IL-2 adrninistered to aged mice for three weeks has been shown to correct the T-ceU functional deficiency associated with antigen-specific immunoglobulin production by certain lymphoid tissue (43). 

The decline in immune function may pardy depend on a deficiency of coenzyme Q, a group of closely related quinone compounds (ubiquinones) that participate in the mitochondrial electron transport chain (49). Concentrations of coenzyme Q (specifically coenzyme Q q) appear to decline with age in several organs, most notably the thymus. 

Biochemical Functions. Ascorbic acid has various biochemical functions, involving, for example, coUagen synthesis, immune function, dmg metabohsm, folate metaboHsm, cholesterol cataboHsm, iron metaboHsm, and carnitine biosynthesis. Clear-cut evidence for its biochemical role is available only with respect to coUagen biosynthesis (hydroxylation of prolin and lysine). In addition, ascorbic acid can act as a reducing agent and as an effective antioxidant. Ascorbic acid also interferes with nitrosamine formation by reacting direcdy with nitrites, and consequently may potentially reduce cancer risk. 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

Chemical-mediated immune suppression has been identified from the experimental study of several wildlife species. Harbour seals fed either chemically contaminated fish from the Wadden Sea or imcontaminated fish were found to have differing immune responses, with the exposed group showing lowered immune response to microbial infections and certain types of cancer. "" Mink fed fish taken from below a discharge point for bleached Kraft pulp mill effluent have also shown impaired immune function, " showing that the non-accnmillative chemicals in this effluent can actively disrupt endocrine associated functions. 

Birds. In avian populations, organochlorine-associated suppression of T-cell mediated immune response has been found in herring gull and Caspian tern colonies adjacent to the Great Lakes in Northern America.In the most severe cases, immune response was suppressed by up to 50%. Similarly, seabirds exposed to petrochemicals from oil spills have been found to have suppressed immune function. " ... 

To study the effect of an increased gene dosage of GR, Reichardt et al. (2000) and van den Brandt et al. (2007) generated rodent models of GR overexpression. These approaches confirmed that GR controls neuronal and immune functions in a dosage-dependent manner. These results highlight the importance of tight control of GR expression in target tissues and may explain... 

Vitamin C status is supposed to play a role in immune function and to influence the progression of some chronic degenerative diseases like atherosclerosis, cancer, cataracts, and osteoporosis. The role of vitamin C in immune function, especially during common cold and upper respiratory tract infection, is the subject of lively debate. The exact mechanisms of action have not yet been fully elucidated, but the results of several trials point to a reduced duration and intensity of infections in subjects consuming high amounts of vitamin C (200-1000 mg/d). However, the incidence of common cold was not influenced significantly (24). 

Also, chronic-duration studies have not generally shown adverse effects on organs of the immune system. Routine gross and histopathologic examination of the lymph nodes and thymus of rats, mice, and dogs exposed to endosulfan for 2 years at doses of up to 2.9 mg/kg/day (Hoechst 1989a), 2.51 mg/kg/day (Hoechst 1988b), and 1 mg/kg/day (EMC 1967), respectively, revealed no adverse effects. However, these studies did not assess immune function directly. 

Since the limited information available on the effects of dermally administered endosulfan suggests that this chemical behaves similarly across both routes of exposure and that adverse effects on immune function end points have also been observed in vitro, there is no reason to suspect that the immunotoxic effects observed following oral exposure are route-specific. Tests of immunologic function in exposed human populations would provide information as to whether immunosuppression also occurs in humans... 

Kenow, K.P., Grasman, K.A., and Hines, R.K. et al. (2007). Effects of methylmercury exposure on the immune function of common loons. Environmental Toxicology and Chemistry 26, 1460-1469. 

Ahn SY, Cho CH, Park KG, Lee HI, Lee S, Park SK, Lee IK, Koh GY (2004) Tumor necrosis factor-alpha induces fractaUdne expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-alpha-induced fractaUdne expression. Am J Pathol 164 1663-1672 Alfano M, Schmidtmayerova H, Amelia CA, Pushkarsky T, Bukrinsky M (1999) The B-oligomer of pertussis toxin deactivates CC chemokine receptor 5 and blocks entry of M-tropic HIV-1 strains, [see comments]. J Exp Med 190 597-605 Ambrosini E, Alois F (2004) Chemokines and glial cells a complex network in the central nervous system. [Review] [239 refs]. Neurochem Res 29 1017-1038 Azuma Y, Ohura K (2002) Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NE-kappaB DNA binding in THP-1 differentiated to macrophagelike cells. Scand J Immunol 56 260-269... 

Volk T, Schenk M, Voigt K, Tohtz S, Putzier M, Kox WJ (2004) Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery. Anesth Analg 98(4) 1086-1092... 

Since initial studies identified opioid receptors on T-lymphocytes (Wybran et al. 1979), the effects of opioids on immune function have been extensively studied. Details of these studies have been exhaustively reviewed (Madden et al. 1991 Adler et al. 1993 Peterson et al. 1998 Donahoe and Vlahov 1998 Roy et al. 2006), and will only be briefly mentioned here. In general, opioids suppress immune function. Peripheral leukocytes, including lymphocytes and peripheral blood mononuclear cells (PBMCs) can express the four major opioid receptor types, MOP, DOP, KOP,... 

Roy S, Wang J, Kelschenbach J, Koodie L, Martin J (2006) Modulation of immune function by morphine imphcations for the susceptability to infection. J Neuroimmune Pharmacol 1 77-89 Sabatier JM, Vives E, Marbrouk K, Benjouad A, Rochat H, Duval A, Hue B, Bahraoui E (1991) Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1. J Virol 65 961-967... 

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