Acute Inflammation and Sleep

Research that began in the 1970s indicates that the host response to microbial infections alters the expression of immune-modulatory substances that also regulate sleep. Various bacterial and viral components both trigger immune responses and elicit alterations in sleep during infection. The quantitative and temporal changes that develop in sleep throughout the course of an infectious disease have been characterized in animals infected with various bacteria, viruses, and parasites. The precise characteristics of infection-related changes in sleep vary with the specific microorganism, the route of infection, the genetic background of the host, and differences in the disease process. For example, rabbits develop different alterations in sleep when infected with Pasteurella multocida via the intravenous route, which causes septicemia, or the intranasal route, which causes pneumonia (Toth and Krueger 1990b). In general, rabbits with bacterial and fungal infections develop an initial increase and a subsequent decrease in the amount of time spent in SWS, whereas rapid eye movement sleep (REMS) is consistently reduced (Toth and Krueger 1989; Toth and Krueger 1990a). Infected rabbits also typically develop fevers, but the fevers generally persist beyond the period of enhanced sleep. In mice, the effects of infection with the fungal organism Candida albicans on sleep and temperature vary depending on the genetic background of the mice (Toth and Hughes, Compar Med, 2006).

The administration of killed bacteria and isolated bacterial components can also alter sleep patterns, and treatment with bacteriocidal antibiotics microbially induced changes in sleep (Toth and Krueger 1988). Administration of bacterial endotoxin alters sleep in both humans and animals (Lancel, Cronlein, Muller-Preuss, and Holsboer 1995; Mathias, Schiffelholz, Linthorst, Pollmacher, and Lancel 2000; Mullington et al. 2000; Schiffelholz and Lancel 2001). In rats, endotoxin administration promotes non-REMS (NREMS) during the dark (active) phase and decreases REMS during both the light and dark phases of the diurnal cycle (Lancel et al., 1995; Mathias et al., 2000; Schiffelholz and Lancel 2001). In humans, endotoxin suppresses REMS and prolongs REMS latency (Korth, Mullington, Schreiber, and Pollmacher 1996; Mullington et al. 2000), but its effects on NREMS depend on the dose and the diurnal time of administration (Mullington et al. 2000). Increases in the amount and intensity of nocturnal NREMS consistently develop only after the administration of subpyrogenic doses of endotoxin given shortly before the normal evening onset of sleep (Korth et al., 1996; Pollmacher, Schuld, Kraus, Haack, Hinze-Selch, and Mullington 2000). Pyrogenic doses disrupt sleep and reduce NREMS (Mullington et al. 2000).

Infection with influenza virus alters sleep in people and animals. Healthy human volunteers experimentally infected with rhinovirus, influenza virus, or both show less sleep during the incubation period, but more sleep during the symptomatic period; sleep quality and the number of awakenings are not affected (Smith 1992). Influenza-infected mice develop alterations in sleep that vary qualitatively and quantitatively depending on the genetic background of the mouse (Toth, Rehg, and Webster 1995; Toth and Verhulst 2003; Toth and Williams 1999c). Several observations suggest that viral replication is necessary to cause prolonged changes in sleep and activity. For example, inoculation of mice with the avian paramyxovirus Newcastle disease virus (NDV), which undergoes only abortive replication in mice, elicits only transient sleep enhancement (Toth 1996). Similarly, inoculation of mice with killed influenza virus does not promote sleep (Toth et al., 1995; Toth and Verhulst 2003). Double-stranded RNA (dsRNA), which is produced in infected host cells during viral replication, may mediate at least some of the somnogenic effects of viral infections. Intracerebroventricular administration of dsRNA induces sleep in rabbits, and synthetic dsRNA (polyinosinic:polycytidilic acid, or poly IC) increases sleep in both rabbits and mice (Kimura-Takeuchi, Majde, Toth, and Krueger 1992a; Kimura-Takeuchi, Majde, Toth, and Krueger 1992b; Toth 1996).

Natural Remedy For Yeast Infections

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