Changes in Spontaneous and LPS-induced ex vivo Cytokine Production and mRNA expression in Male and Female Athletes Following Prolonged Exhaustive Exercise

Abstract

Purpose: The capacity of whole blood cultures to produce cytokines in response to endotoxin (LPS) was studied in athletes before, 30 min after, 3 h after and 24 h after a half-marathon run. Methods: Eight well trained men and 8 well trained women (6 of them in the late luteal phase of their cycle) participated. EDTA blood was incubated with or without LPS for 1 h, and cytokine concentration and gene expression were determined. To quantify LPS-dependent release on a per monocyte basis (LDR), the mean values of the difference (delta) between cytokine concentration in stimulated and unstimulated cultures, normalized to monocyte numbers, were calculated. Results: LDR of TNF-alpha was significantly reduced by exercise with identical kinetic in men and women. TNF-alpha mRNA expression was slightly down-regulated following exercise (P<0.05), but significantly so only in women. LDR of IL-6 was also reduced, but with a faster kinetic in women than in men. Similarly, 30 min post-exercise; LDR and spontaneous release of IL-1ra were significantly less in women than men. Concomitantly, IL-1ra mRNA was significantly elevated in unstimulated and in stimulated cultures in men only. IL-10 and IL-10 mRNA were significantly induced 30 min following exercise in absence of any detectable LDR. Women showed significantly lower levels than men. LDR and spontaneous release of IL-8 was enhanced in men and TGF-beta 1 in women. A significant up-regulation was seen in unstimulated IL-8 mRNA for women and LPS-stimulated IL-8 mRNA expression for men following exercise. Conclusion: Altogether, LPS-dependent ex vivo cytokine release was strongly influenced by exercise and these changes could only in part be attributed to changes in messenger RNA. Results for IL-1ra, IL-6 and IL-10 pointed to a less pronounced anti-inflammatory response in women as compared with men. Our results also indicate an early production of IL-10 by peripheral blood cells in response to exercise.