Acute infection and inflammation are the most evident situations that demonstrate the effects of cytokines on the brain, although very little detailed information is available on the circulating amounts of TNF-a and IL-6 during infection and inflammation besides the acute phase of sepsis. Moreover, there is a range of other clinical conditions where peripheral cytokine signals might modulate complex human brain functions. Numerous studies showed that the therapeutic administration of cytokines for the treatment of hepatitis, multiple sclerosis, or rheumathoid arthritis can induce depressive symptomatology, which widely overlaps with the syndrome of "sickness behavior" observed in animal models of infection and inflammation. However, in these clinical situations and during acute febrile infections the amounts of circulating inflammatory cytokines are huge, usually two orders of magnitude or more above baseline levels. In contrast, circulating levels are only slightly or moderately increased in the most frequent clinical situations where cytokines might play a role in inducing symptoms of depression, such as chronic infection or inflammation, cancer, cardiovascular disease, and autoimmune disorders (Yirmiya et al. 2000). Unfortunately, the studies on cytokine levels in patients with autoimmune diseases, chronic inflammation and infection are rare and conflicting, in particular with respect to longitudinal investigations (e.g., Mangge, Gallistl, and Schauenstein 1999). Independently from these disorders involving definite immunopathology, slightly increased levels of cytokines have been hypothesized to be involved in the pathophysiology of major depressive disorders in otherwise healthy people (Smith 1991). In recent years, it has become evident that inflammatory processes play an important role in cardiovascular disease and heart failure. Slightly increased TNF-a and possibly also IL-6 levels are often found in patients with heart disease (Ferrari 1999). A number of psychotropic drugs induce slight increases in the circulating levels of TNF-a, IL-6, or both, which are in the same range as those seen in patients with heart disease (Haack, Hinze-Selch, Fenzel, Kraus, Kuhn, and Pollmacher 1999). Unfortunately, only few studies addressed the physiological relevance of circulating inflammatory cytokines or of slight to moderate increases in their levels with respect to central nervous function. The present review focuses on changes in sleep, memory, mood, and food intake following the experimental administration of bacterial endotoxin to healthy volunteers.
Was this article helpful?