Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which include fatigue, myalgia, and low-grade fever, are similar to those experienced 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-1 receptor antagonist (IL-1Ra), and soluble interleukin-1 receptor type II (IL-1sRII) is abnormal in female CFS patients compared to age- and activity-matched controls; (2) that these abnormalities may be evident only at certain times in the menstrual cycle; and (3) that physical exertion (stepping up and down on a platform for 15 min) may accentuate differences between these groups.

Isolated peripheral blood mononuclear cells from healthy women, but not CFS patients, exhibited significant menstrual cycle-related differences in IL-1 beta secretion that were related to estradiol and progesterone levels (R2 = 0.65, P < 0.01). IL-1Ra secretion for CFS patients was twofold higher than controls during the follicular phase (P = 0.023), but luteal-phase levels were similar between groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients compared to controls (P = 0.002). 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).

These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradiol and progesterone. Furthermore, the increased release of IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated with chronic, low-level activation of the immune system.

 

Source: Cannon JG, Angel JB, Abad LW, Vannier E, Mileno MD, Fagioli L, Wolff SM, Komaroff AL. Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome. J Clin Immunol. 1997 May;17(3):253-61. http://www.ncbi.nlm.nih.gov/pubmed/9168406

 

Clinical laboratory test findings in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects.

METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests.

RESULTS:Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful.

CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Comment in: Clinical laboratory test findings in patients with chronic fatigue syndrome. [Arch Intern Med. 1995]

 

Source: Bates DW, Buchwald D, Lee J, Kith P, Doolittle T, Rutherford C, Churchill WH, Schur PH, Wener M, Wybenga D, et al. Clinical laboratory test findings in patients with chronic fatigue syndrome. Arch Intern Med. 1995 Jan 9;155(1):97-103. http://www.ncbi.nlm.nih.gov/pubmed/7632202

 

Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome

Erratum in: Med Hypotheses 1995 Aug;45(2):219.

 

Abstract:

Abnormalities of Essential Fatty Acid (EFA) incorporation into phospholipid are found in chronic diseases. More recently changes in circulating EFA metabolites (EFAM) together with EFAM hypo-responsiveness of immune cells and EFAM production from cells have been found associated with disease.

We hypothesize that changes in ratio of EFAMs are the normal physiological responses to stressors, but when stressors are excessive or prolonged, EFAM systems may become unpredictably hypo-responsive owing to factors such as receptor down regulation and substrate depletion. In time, many homeostatic system become deranged and held in that state by minor stressors.

Literature review of chronic fatigue syndrome (CFS) shows hyper and hypo-responsiveness in immune function, several Hypothalamo-Pituitary (HP) axes and sympathetic nervous system, all relatable to dysfunctional changes in EFA metabolism.

For the first time, we explain chronic immune system activation and hypo-responsive immune function in CFS; through EFAMs. Dietary EFA modulation (DEFA) can alter ratios of both membrane EFAs and produced EFAMs, and if maintained can restore hypo-responsive function.

We discuss dietary strategies and relevance in CFS, and a case series of CFS patients applying DEFA with other titrated published managements which saw 90% gaining improvement within 3 months and more than 2/3 fit for full time duties. This hypothesis and DEFA may have relevance in other chronic conditions.

 

Source: Gray JB, Martinovic AM. Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome. Med Hypotheses. 1994 Jul;43(1):31-42. http://www.ncbi.nlm.nih.gov/pubmed/7968718