INTERLEUKIN-1-BETA, INTERLEUKIN-1 RECEPTOR ANTAGONIST, AND SOLUBLE INTERLEUKIN-1 RECEPTOR-TYPE-II SECRETION IN CHRONIC-FATIGUE-SYNDROME

Chronic fatigue syndrome is a condition that affects women in dispropo rtionate numbers, and that is often exacerbated in the premenstrual pe riod and following physical exertion. The signs and symptoms, which in clude fatigue, myalgia, and low-grade fever, are similar to those expe rienced by patients infused with cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular secretion of interleukin-1 beta (IL-1 beta), interleukin-l receptor a ntagonist (LL-1Ra), and soluble interleukin-l receptor type II (IL-1sR II) is abnormal in female CFS patients compared to age- and activity-m atched controls; (2) that these abnormalities may be evident only at c ertain times in the menstrual cycle; and (3) that physical exertion (s tepping up and down on a platform for 15 min) may accentuate differenc es between these groups. Isolated peripheral blood mononuclear cells f rom healthy women, but not CFS patients, exhibited significant menstru al cycle-related differences in IL-1 beta secretion that were related to estradiol and progesterone levels (R-2 = 0.65, P < 0.01). IL-1Ra se cretion for CFS patients was twofold higher than controls during the f ollicular phase (P = 0.023), but luteal-phase levels were similar betw een groups. In both phases of the menstrual cycle, IL-1sRII release wa s significantly higher for CFS patients compared to controls (P = 0.00 02). The only changes that might be attributable to exertion occurred in the control subjects during the follicular phase, who exhibited an increase in IL-1 beta secretion 48 hr after the stress (P = 0.020). Th ese results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradio l and progesterone. Furthermore, the increased release of IL-1Ra and s IL-1RII by cells from CFS patients is consistent with the hypothesis t hat CFS is associated with chronic, low-level activation of the immune system.