Chronic exercise and the pro-inflammatory response to endotoxin in the serum and heart.

Purpose: To examine the effects of moderate intensity chronic exercise on tumor necrosis factor-alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) responses to endotoxin in female Sprague-Dawley rats.

Methods: Rats were divided into two groups, exercise (n=17) and sedentary (n=24). Exercise (Ex) rats completed 12 weeks of motorized treadmill running 3 days/week for 15-25 min at 22-25 m/min, while sedentary (Sed) rats remained in their cages. Twenty-four hrs after the last exercise session, animals were subdivided into three groups. One subgroup served as baseline controls. These rats received an injection of saline (s) and were killed immediately (Sed-s and Ex-s), while the other groups received an injection of lipopolysaccharide (LPS). LPS animals were killed 2 h (Sed-L2 and Ex-L2) or 4 h after the LPS injection (Sed-L4 and Ex-L4).

Results: Serum TNFalpha was elevated 2 h after LPS injection in both Sed and Ex groups, but was significantly higher in the chronic exercise group (Ex-L2 versus. Sed-L2). Similarly, serum beta glucuronidase activity, an indicator of tissue damage, was elevated 2 and 4 h after LPS injection, and was significantly higher in the exercise groups. Post-treatment left ventricular TNFalpha and iNOS activity, as well as stable nitric oxide derivatives in the serum (NOx), were significantly higher in LPS-injected groups compared to saline groups, but no difference in LPS effect was observed between sedentary and exercise groups.

Conclusions: Moderate intensity chronic exercise stress caused an exaggerated serum TNFalpha response to endotoxin and an elevation in a serum marker of LPS-induced tissue damage.