Immune function, modulation

Replacement of the urethane carbonyl function by an aromatic ring leads to a benzo-thiazole that is described as an immune function modulator. In an analogous approach to that used above, anilinothiol (63-1) is condensed with the thiocarbamoyl chloride (63-2) again in the presence of a base. This leads directly to frentizole (63-3) [66]. 

Early studies revealed that ginseng possesses biomodulatory effects on the higher centers of the central nervous system, facilitating both physical and mental activities. It has a noteworthy effect on the endocrine system, regulating the blood sugar level as demonstrated in alloxan diabetics. Recent experimental and clinical studies concluded that it has a wide range of effects, such as a remarkable anti-shock effect in circulatory failure, modulatory effects on the immune functions, modulation of cellular metabolic processes, modulation of neuroendocrine system activities, improvement of learning and memory processes, and others (see Tab. 12). 

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... 

A wide diversity of herbal remedies have purported abilities to stimulate defense functions. Complexes of carbohydrate and lignin, which are present in some herbs, modulate enteric immune functions (Kiyohara et al, 2000), and the changes in cytokine secretion (Matsumoto and Yamada, 2000) can trigger systemic responses. The polysaccharides present in other herbal medicines augment production of immunoglobulin (Ig) A by the Peyer s patches in the small intestine (Sakushima et al, 1997 Yu et al, 1998). The responses of the enteric immune system to lectins are variable (Pusztai 1993), and can elicit systemic responses (Lavelle et al, 2000). Other phytochemicals provide protection by inducing detoxification pathways in mucosal cells (Williamson et al, 1998). 

Blount, J. D., Metcalfe, N. B., Birkhead, T. R., and Surai, P. F. 2003. Carotenoid modulation of immune function and sexual attractiveness in zebra finches. Science 300 125-127. 

Teichmann, J.V. et al., Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia, J Interferon Res, 8, 15, 1988. 

Lysle, D.T., Luecken, L.J., and Maslonek, K.A., Modulation of immune function by a conditioned aversive stimulus Evidence for the involvement of endogenous opioids, Brain, Behav. Immun., 6, 179, 1992. 

The sympathetic nervous system (SNS) and the hypothalamic-pituitary axis work together as important modulators of the immune system after exposure to stressors. Norepinephrine (NE) and epinephrine (EPI) (catecholamines from the SNS) and neuroendocrine hormones modulate a range of immune cell activities, including cell proliferation, cytokine and antibody production, lytic activity, and migration. This chapter will focus on these two major pathways of brain-immune signaling, briefly summarizing the evidence for SNS and hypothalamic-pituitary-adrenal (HPA) modulation of immune function, their influence on immune-mediated diseases, immune modulation in aging, and early life influences on these pathways. 

Bellinger, D.L. et al., Aging and sympathetic modulation of immune function in Fischer 344 rats Effects of chemical sympathectomy on primary antibody response, J. Neuroim-munol., in press, 2005. 

THC and Other Cannabinoids Induced Modulation of Immune Functions in vivo and in vitro... 

At least some of the cannabinoid-induced modulation of immune cells, and effects on host resistance to infection, are mediated directly by binding of cannabinoids to CBRs, particularly CBR2. Host immunity to microbes, however, involves many cell types, both immune and non-immune, as well as soluble factors including cytokines, chemokines, neurocytokines, and hormones related to the HP axis. It is therefore likely that a variety of cellular and molecular mechanisms whereby cannabinoids, including THC, affect immune function. 

Opiates-Induced Modulation of Immune Functions In Vivo and In Vitro... 

Klein, T., Friedman, H, Modulation of murine immune cell function by marijuana components, in Drugs of Abuse and Immune Function, Watson, R. CRC Press, Boca Raton, FL, 1990, pp. 87-111. 

Awareness of immunotoxicology was stimulated by a comprehensive review by Vos in 1977, in which he provided evidence that a broad spectrum of xenobiotics alter immune responses in laboratory animals and subsequently may affect the health of exposed individuals. Several additional reviews, as well as national and international scientific meetings, have reinforced these early observations. In several studies, alteration of immune function was accompanied by increased susceptibility to challenge with infectious agents or transplantable tumor cells, indicating the resulting immune dysfunction in altered host resistance. Clinical studies in humans exposed to xenobiotics have confirmed the parallelism with immune dysfunction observed in rodents. The latter sections in this volume describe studies with xenobiotics that resulted in immune modulation in rodents and man. 

It is difficult to simulate in vitro the interaction of all of the various cell types and modulators of immune function that make up the in vivo system. 

Babu S. Blauvelt CP. Kumaraswami V. Nutman TB Diminished T cell TLR expression and function modulates the immune response in human filarial infection. J Immunol 2006 176 3885-3889. 

CN166 Puertollano, M. A., M. A. de Pablo and G. Alvarez de Gienfuegos. Relevance of dietary lipids as modulators of immune functions in cells infected with Listeria monocytogenes. Clin Diagn Lab Immunol 2002 9(2) 352-357. 

New advances in boron nntrition research shonld include better characterization of the mechanisms through which boron modulates immune function and insulin release (Hunt 1998). Epidemiological studies should be initiated to identify health conditions associated with inadequate dietary boron (Sutherland et al. 1998). Finally, Dourson et al. (1998) recommend more research on uncertainty factors used in establishing tolerable daily intake values for the protection of human health, with emphasis on variations in interspecies and intraspecies differences in resistance to boron. 

Sanbongi C, Suzuki N, Sakane T. 1997. Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in-vitro. Cell Immunol 177 129-136. 

Cytokines are a potential way to modify the immune system in several situations because of their ability to act as immunoregulatory chemicals. For example, cytokines such as interferon-alpha and interleukin-2 can be administered to treat certain forms of cancer (see Chapter 36). Likewise, certain interferons can help control viral infections, and interferon-beta may be helpful in autoimmune diseases such as multiple sclerosis (see Chapter 34). Researchers continue to investigate how immune function can be manipulated to treat various diseases, and additional immune system modulators will almost certainly be forthcoming. 

The opioids may modulate the actions of the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. Natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. In general, these effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids. 

---