O Co

Hours After Tailshock

Figure 1. Cote bodv temperature measured during inescapable tailshock and home cagc control (HCC) treatment, as well as 1^4 and 20-24 hr after treatment. BL = Baseline, SK - Shock.

the psychological nature of stress. Ill us we have measured white blood cells, the carrier protein corticosteroid binding globulin (CBG). seromucoids (a measure of acute phase proteins that is predominantly al-acid glycoprotein), and the acute phase protein haptoglobin in blood samples taken 24hr after IS or control treatment. As can be seen in Fig. 2, exposure to IS led to the typical pattern produced by pathogens (Deak, Meri-weather, Fleshner, Spencer, Moldawcr, Grahn, Watkins, & Maier., 1997). A final aspect that we have studied involves basal levels of plasma corticosteroids. We have shown that the administration of inflammatory agents increases basal corticosteroid levels for a number of days and IS also increases basal corticosteroids measured 24 and 48 hr after IS (Fleshner, Deak, Spencer, Laudenslagcr, Watkins, & Maier, 1995).

It has already been noted that the administration of IL-1 into brain induces the outflow of some product or process from brain that can directly, or through the induction of further products, impact on liver function. The results described above suggest that this is so for IS as well. The cascade of processes initiated by pathogens begins with the macrophage and other immune cell types, and the sickness responses arc driven by cytokines and other substances that are produced by these cells during infection. The 2hr IS session produces fever, acute phase protein increases, and other aspects of sickness that persist for a number of days, well beyond the duration of the stressor. A variety of mechanisms that would lead to this persistent response could be envisaged, but one would involve a prolonged activation of macrophages. This would lead to the long-term production of macrophage products that drives sickness during '"normal infection".

Activated macrophages produce a variety of products. Nitric oxide (NO) has


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