Immune alterations

Nelson CJ, Carrigan KA, Lysle DT (2000) Naltrexone administration attenuates surgery-induced immune alterations in rats. J Surg Res 94(2) 172-177 Noel RJ Jr, Kumar A (2006) Virus replication and disease progression inversely correlate with SIV tat evolution in morphine-dependent and SIV/SHIV-infected Indian rhesus macaques. Virology 346(1) 127-138... 

Undeger U, Basaran N, Canpinar H, et al. 1996. Immune alterations in lead-exposed workers. Toxicology 109(2-3) 167-172. 

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]). 

Lysle, D.T.,et al., Characterization of immune alterations induced by a conditioned aversive stimulus, Psychobiology, 18, 220, 1990. 

Pb exposure at low to moderate levels appears to alter T lymphocyte responses in such a way as to increase the risk of atopic disease and some forms of autoimmunity. Increased IgE production following exposure to Pb is among the most frequently reported immune alteration, suggesting that Pb is a possible risk factor for allergic asthma [33, 34, 40, 91, 92] as well as later life allergic disease [32],... 

Keil, D.E., et al., Comparison of JP-8 induced immune alterations following two different routes of exposure in female B6C3F1 mice, Toxicologist 66, 145, 2002. 

Chung, H.-T. et al., Involvement of prostaglandins in the immune alterations caused by the exposure of mice to ultraviolet radiation, J. Immunol. 137, 2478-2484, 1986. 

While the database for developmental immunotoxicants is relatively modest, several chemicals have received considerable research attention. For example, Luebke et al. (2004), in a report to the USEPA, reviewed the comparative age-related sensitivities of the human and rodent immune systems for four developmental immunotoxicants DES, lead, diazepam, and tributyltin. These authors concluded that DES, a strong estrogenic compound, produced similar immune alterations at similar doses following exposure of adult rodents and embryos or neonates. However, the immune changes persisted following early exposure, whereas adults appeared to be able to recover post-exposure. 

Adverse effects Long-term use of infliximab is associated with development of anti-infliximab antibodies unless the drug is used in combination with methotrexate. Infusion reactions such as fever, chill, pruritus, or urticaria have occurred. Infections leading to pneumonia, cellulitis, and other conditions have also been reported. Whether treatment with infliximab predisposes to lymphoma, a condition that occurs with immunosuppressive or immune-altering drugs, remains to be established. 

Zerva LV, Constantopoulos SH, Moutsopoulos HM. 1989. Humoral immunity alterations after environmental asbestos exposure. Respiration 55 237-241. 

As indicated by this brief overview there is considerable evidence for a close relationship between changes in the immune system and depression, particularly MDD. Whether there is a clear cause and effect relationship between these is not known in most cases, although there are sdrong data in the case of IL-6 and IFN-a, as noted. It will be important to determine more clearly the exact relationship between depression and immune system alterations. There is also a need to determine which of the immune alterations that are found are clinically important (Irwin, 2001). 

Vojdani A, Ghoneum M, Brautbar N. 1992. Immune alteration associated with exposure to toxic chemicals. Toxicol Ind Health 8 239-254. 

Perinatal exposure to PCBs also has been associated with alterations in immunocompetence in children (Dewailly et al. 2000 Smith 1984 Weisglas-Kuperus 2000 Weisglas-Kuperus et al. 1995). These children should continue to be observed for any indication of reduced immunocompetence which may potentially lead to increased incidence of illnesses. The findings of immune alterations following PCB... 

A variety of immune alterations have been reported in humans and laboratory animals exposed to other heavy metals, depending on the dose, duration, and route of exposure and genetic susceptibility (Koller, 1980 Ohsawa, 1993 IPCS, 1996). In many studies of subchronic or chronic exposure, non-essential heavy metals such as cadmium, lead, and mercury were immunosuppressive in animals and consequently decreased host resistance to infectious agents and tumours. Immunostimulation has also been shown to occur at levels... 

Although a substantial number of animal data demonstrate numerous immune alterations following in utero exposure to diethylstilbestrol, including abnormal B cell and T cell responses... 

Autoimmune-like phenomena in Brown Norway rats induced by mercuiy(II) chloride peak around day 10 after the last of five subcutaneous injections. After 20 days, immune alterations are mostly at control level, and the kidney effects (e.g. proteinuria) are clearly less than on day 10 (Aten et al., 1988). In addition, low-dose pretreatment of Brown Norway rats with mercuiy(II) chloride prevents development of adverse immunity (Szeto et al., 1999), and neonatal injection of mercury(II) chloride in Brown Norway rats renders them tolerant to mercury-induced (but not gold-induced) autoimmune phenomena (Field et al., 2000). These phenomena, transience of autoimmune effects as well as low-dose protection, are shown to be due at least in part to the development of regulatory immune cells. In the case of mercury(II) chloride, these cells have been identified as either IFN-y-producing CD8+CD45RC high regulatory T cells (Pelletier et al., 1990 Mathieson et al., 1991 Szeto et al., 1999 Field et al., 2003) or RT6.2+ T cells (Kosuda et al., 1994). In view of this, it is relevant to note that Lewis rats that produce predominantly CD8+ regulatory T cells ( suppressor T cells) in response to mercury(II) chloride are resistant to mercury-induced autoimmunity and instead display a polyclonal immunosuppressive response (Pelletier et al., 1987). Based on these differences in strain sensitivity, it is clear that susceptibility to mercury-induced autoimmune effects is dependent on MHC class II haplo-type (Aten et al., 1991). 

Kozhevnikova G, Kuzmin I, Roumak V, Karaulov A (1991) Immune alteration in South Vietnamese exposed to Agent Orange. In Dioxin 91 — Proceedings of the 11th international symposium on chlorinated dioxins and related compounds. Research Triangle Park, North Carolina, p 117. 

McConnachie PR Zahalsky AC (1992) Immune alterations in humans exposed to the termiticide technical chlordane. Arch Environ Health, 47(4) 295-301. 

Dean JH, Luster MI, Boorman GA, Luebke RW, Lauer LD. Application of tnmor, bacterial, and parasite susceptibility assays to study immune alterations induced by environmental chemicals. Environ Health Perspect 1982 43 81-87. 

Exposure to pesticides can provoke a variety of immune reactions. These reactions can be classified into (a) modulation of normal immune responses (immune dysfunction), characteristically manifested as immunosuppression, and (b) pathological enhancement of the immune response, most often manifested as hypersensitivity or autoimmunity. The number of reviews on this subject underscores the interest in and concern for the potential of pesticides to alter immune function (8-15). The two general categories of immune alterations induced by pesticides are discussed below. 

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