Alterations in immune function

Adverse kidney effects have been reported in rats exposed to lead during development (Fowler et al. 1980). Also, alterations in immune function have been observed in young rats exposed to lead perinatally (Faith et al. 1979 Luster et al. 1978). These studies are discussed in more detail in Sections 2.2.3.2 and 2.2.3.3. 

FIGURE 4.1 Scenarios by which chemicals, drugs and other xenobiotics may lead to alterations in immune function. 

In addition, the likelihood that depression represents a complex of disease states with varying involvement of the immune system supports the idea that there is a subgroup of depressed patients who have associated alterations in immune function. Indeed, data suggest that different types of depression display distinct, and even opposite, changes in neuroimmune functions (Antonijevic, 2006). As a result of multiple issues, there are contradictory, or at least inconsistent, findings in the literature. This is characteristic of most types of studies of depression, again probably because depression represents multiple disease states. 

Several nonpeptide delta opioid receptor antagonists are currently under investigation in this project, including 7-benzylidene-7-dehydronaltrexone HCl (BNTX), naltrindole (NTI), and naltriben (NTB). In vitro exposure to BNTX or NTI results in immunosuppression at concentrations between 0.1 and 10 M, consonant with the hypothesis that delta opioid receptor agonists enhance, but delta receptor antagonists suppress, immune functional parameters. In comparison, in vitro exposure to NTB did not result in any detectable alteration in immune function. 

Seveso, Italy, caused wide-spread pollution of the industrial site as well as its surroundings. Serious effects of dioxin were detected both in dontestic animals, such as cows and sheep, and in humans, the most serious early effects being a serious skin disease, chloracne, and alterations in the function of the immune system. Follow-up studies have demonstrated that this accident also increased the cancer risk in exposed individuals. ... 

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. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

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