An inflammatory response to many pathogens is generally characterized by redness, swelling, heat, and pain at the site of infection. These symptoms depend on a constellation of events including, but not limited to, proin-flammatory cytokines (e.g., IL-1, IL-6, tumor necrosis factor-a), and leukocyte trafficking. There have been numerous studies that have examined the influence of psychological stress on the early, inflammatory events that are initiated upon HSV infection. For example, using a murine model, restraint stress was shown to decrease both type I and II interferon production in response to a primary, HSV-1 dermal infection (Ortiz et al., 2003). Furthermore, this decrease in interferon production correlated with an increase in virus titer at the site of primary infection. In another study, hyperther-mic stress was shown to increase the levels of both IL-6 mRNA and the protein itself in the trigeminal ganglia of HSV-1 latently infected mice (Noisakran et al., 1998).The observed stress-induced increase in the expression of this proinflammatory cytokine was shown to be mediated by gluco-corticoids, because the administration of cyanoketone, a corticosterone synthesis inhibitor, blocked this stress-induced increase in IL-6 (Noisakran et al., 1998). More importantly, additional studies demonstrated a potential role for stress-induced increases in IL-6 in HSV pathogenesis. In these studies, latently infected mice, as a result of a previous corneal infection, demonstrated reactivated virus after exposure to hyperthermic stress (Kriesel et al., 1997), and this reactivation was due, in part, to IL-6. In contrast, other studies (Bonneau et al., 1998) have shown that stress, administered in the form of restraint during the primary footpad HSV infection, actually suppresses splenic IL-6 production in an adrenal-dependent manner.
The above studies suggest that psychological stress can modulate the proinflammatory response to an HSV infection. The precise effects of stress on this response may depend on a number of variables including the location at which the response is being measured (peripheral, lymphoid, central nervous system) and the stage of infection (primary vs. latent) of the response. However, it is important to note that, in some circumstances, an inflammatory response may be desirable, whereas in other circumstances it may result in immunopathology and thus be detrimental to the host.
Was this article helpful?