Natural killer cell activity

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Immunotoxicity. The data in humans are limited to a few studies of immune function in lead workers and a study of firearm instructors. In both type of studies, inhalation is assumed to be the primary route of exposure. One study reported significant suppression of IgA levels (Ewers et al. 1982). Another study indicated that serum immunoglobulin levels were not significantly altered (Alomran and Shleamoon 1988). Another large study examined several parameters of immune function (serum immunoglobulins, PHA response, and natural killer cell activity) and found no differences in exposed workers and controls (Kimber et al. 1986b). The study of firearm instructors found functional impairment of cell-mediated immunity in subjects with PbB levels >25 pg/dL (Fischbein et al. 1993). A recent study that evaluated a... 

Santos, MS, Meydani, SN, Leka, L, Wu, DY, Fotouhi, N, Meydani, M, Hennekens, CH, and Gaziano, JM, 1996. Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation. Am J Clin Nutr 64, 772-777. 

Chowdhury, B.A. and R.K. Chandra. 1989. Effect of zinc administration on cadmium-induced suppression of natural killer cell activity in mice. Immunolog. Lett. 22 287-292. 

Selgrade, M.K., Daniels, M.J. and Dean, J.H., Correlation between chemical suppression of natural killer cell activity in mice and susceptibility to cytomegalovirus rationale for applying murine cytomegalovirus as a host resistance model and for interpreting immunotoxicity testing in terms of risk of disease, J. Toxicol. Environ. Flealth, 37, 123, 1992. 

Wilson, S.D. et al., Correlation of suppressed natural killer cell activity with altered host resistance models in B6C3F1 mice, Toxicol. Appl. Pharmacol., 177, 208, 2001... 

Levy, S. M. et al., Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity, Nat. Immun, Cell. Growth Regul., 10, 289, 1991. 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

Novick, D.M. et al., Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients, J. Pharmacol. Exp. Ther., 250, 606, 1989. 

Perez, L. and Lysle, D.T., Corticotropin-releasing hormone is involved in conditioned stimulus-induced reduction of natural killer cell activity but not in conditioned alterations in cytokine production or proliferation responses, J. Neuroimmunol., 63, 1, 1995. 

Saurer, T. B. et al., Suppression of natural killer cell activity by morphine is mediated by the nucleus accumbens shell, J. Neuroimmunol., 173, 3, 2006. 

Yun, Y.S. et al., Effect of red ginseng on natural killer cell activity in mice with lung adenoma induced by urethan and benzo(a)pyrene, Cancer Detect Prev Suppl, 1, 301, 1987. 

Kalland, T., Forsberg, J.G. Natural killer cell activity and tumor susceptibility in female mice treated neonatally with diethylstilbestrol, Cancer Res. 51, 134, 1981. 

Several cytokines have been characterized at the molecular level in different species of marine mammals (Table 23.2). In addition, limited evidence exists for conserved functionality of cytokines in marine mammals, such as the ability of human recombinant IL-2 to stimulate T cell proliferation [32, 33] and natural killer cell activity [39,40] in beluga whales and harbor seals. Assays were developed to quantify circulating levels of cytokines [41,42], as well as C-reactive protein, a marker of acute inflammation [43],... 

De Guise, S. et al., Immune functions in beluga whales (Delphinapterus leucas) evaluation of natural killer cell activity, Vet. Immunol. Immunopathol., 58, 345, 1997. 

Coe, C.L. and Erickson, C., Stress decreases natural killer cell activity in the young monkey even after blockade of steroid and opiate hormone receptors, Dev. Psychobiol., 30, 1, 1997. 

Bonneau, R. H. et al., Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection, Brain Behav. Immun., 5, 170, 1991. 

Hunzeker, J. et al., Modulation of natural killer cell activity by restraint stress during an influenza A/PR8 infection in mice, Brain Behav. Immun., 18, 526, 2004. 

Assessment of pulmonary immunocompetence was determined by exposing male Fischer 344 rats to phosgene at 0.1, 0.5, or 1 ppm for 4 h and measuring pulmonary natural killer cell activity on day 1, 2, 4, or 7 postexposure (Burleson and Keyes 1989). The animals were exposed in a Rochester cham... 

The in vivo antitumor effects of interferons are believed to be related to both augmentation of natural killer cell activity and antiproliferative effects. Antiproliferative activity probably also accounts for the bone marrow suppression observed in some individuals given IFN and could potentially produce effects in a routine preclinical reproduction or teratology evaluation. Dosing studies performed in... 

Nonspecific immunity Natural killer cell activity... 

Riccardi, C., Puccetti, P., Santoni, A. and Herberman, R.B. (1979). Rapid in vivo assay of mouse natural killer cell activity. J. Natl. Cancer Inst. 63 1041-1045. 

GO) leukocyte counts, natural killer cell activity, and Concanavlin A responsiveness) ... 

Robertson, L.E., Denny, A.W., Huh, Y.O., Plunkett, W., Keating, M.J., and Nelson, J.A., Natural killer cell activity in chronic lymphocytic leukemia patients treated with fludarabine, Cancer Chemother. Pharmacol., 37, 1996, 445-450. 

Malorni, W., Straface, E., Di Genova, G., Fattorossi, A., Rivabene, R., Camponeschi, B., Masella, R., and Viora, M., 1997, Oxidized low-density hpoproteins affect natural killer cell activity by impairing cytoskeleton function and altering the cytokine network, Exp. Cell Res. 236 436-445. 

Stress is frequently a trigger factor for depression in vulnerable patients. There is clinical evidence to show that CRT is elevated in the cerebrospinal fluid of untreated depressed patients, which presumably leads to the hypercortisolaemia that usually accompanies the condition. One of the consequences of elevated plasma glucocorticoids is a suppression of some aspects of cellular immunity. It is now established that many cellular (for example, natural killer cell activity, T-cell replication) and non-cellular (for example, raised acute phase proteins) aspects are abnormal in the untreated depressed patient. Such observations could help to explain the susceptibility of depressed patients to physical ill health. 

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