CYTOKINE RELEASE AND ITS MODULATION BY DEXAMETHASONE IN WHOLE-BLOOD FOLLOWING EXERCISE

Glucocorticoids (GC) play an important role in the treatment of inflam matory diseases like asthma. However, in selected patients a relative resistance to GC has been reported. Recently, it has been suggested th at GC sensitivity of peripheral blood leucocytes may be regulated in a dynamic fashion during exercise, in association with activation of th e hypothalamic-pituitary-adrenal (HPA) axis. The aim of the present st udy was to explore changes in the GC sensitivity of cytokine productio n by leucocytes following strenuous exercise by well trained oarsmen. These changes were studied using lipopolysaccharide (LPS)-induced and anti-CD2/anti-CD28 MoAb-stimulated cytokine release in whole blood and its modulation by dexamethasone. Following exercise, significant decr eases in LPS-induced release of IL-6, tumour necrosis factor-alpha (TN F-alpha) and IL-IO and anti-CD2/anti-CD28 MoAb-stimulated secretion of interferon-gamma (IFN-gamma) were observed. In addition, the inhibito ry effect of dexamethasone on both IL-6 and TNF-alpha secretion was si gnificantly reduced following exercise, whereas that on IL-10 and IFN- gamma release was not affected. These exercise-induced changes were ac companied by activation of the HPA axis, as indicated by an increase i n circulating adrenocorticotropic hormone (ACTH) levels immediately fo llowing exercise. The results from the present study suggest that GC s ensitivity of whole blood cytokine release can be regulated in a dynam ic fashion and that this can be assessed using an ex vivo stimulation assay. Moreover, since dexamethasone responsiveness of anti-CD2/anti-C D28 MoAb-induced IFN-gamma secretion in whole blood is not affected by exercise, it may suggest that exercise differentially affects monocyt es and lymphocytes. The dynamic regulation of steroid responsiveness o f leucocytes, as observed in the present study, could have important c onsequences for the effectiveness of GC treatment in inflammatory dise ases.