Opiates, Stress, and Immunity: Animal Studies

Recent evidence suggests that psychological and environmental factors, acting through the central nervous system, can alter immune function and render an organism more vulnerable to certain diseases, including neoplasia. This article begins with a brief review of the literature concerning the interactions between the nervous, endocrine, and immune systems. We continue with recent data from our laboratory studying the interactions between stress, opioid peptides, and immune function. We found that a particular form of footshock stress, known to activate endogenous opioid systems, can suppress immune function and enhance tumor growth in rats. These data suggest that the tumor-enhancing effect of stress might be mediated by its immune-suppressive actions. We also found that inescapable but not escapable tail shock suppressed NK activity in rats. Thus, the same amount of shock had different outcomes depending on the degree of control available to the animal. That all these stress-induced effects were blocked by the opioid antagonists suggests their mediation by opioid peptides. Supporting this hypothesis, we found that the effects of stress can be mimicked by a single high dose of morphine given systemically or by a vastly smaller dose given directly into the brain. These results imply that the effect of morphine on the immune system is mediated by brain opioid receptors. More generally, these data support the view that the nervous system can modulate the immune system and exercise significant control over disease processes, perhaps by activating endogenous opioid systems.