Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome

Abstract:

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase.

Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion.

For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls.

In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively).

These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

 

Source: Cannon JG, Angel JB, Abad LW, O’Grady J, Lundgren N, Fagioli L, Komaroff AL. Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome. J Clin Immunol. 1998 Jul;18(4):291-8. http://www.ncbi.nlm.nih.gov/pubmed/9710746

 

Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin. Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia.

We compared levels of GH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), insulin, and C-peptide in nondepressed CFS patients and normal controls. We found attenuated basal levels of IGF-I (214 +/- 17 vs. 263.4 +/- 13.4 micrograms/L, p = .036) and IGF-II (420 +/- 19.8 vs. 536 +/- 24.3 micrograms/L, p = .02) in CFS patients and a reduced GH response to hypoglycemia (peak GH; 41.9 +/- 11.5 vs. 106.0 +/- 25.6 mU/L, p = .017). Insulin levels were higher (7.6 +/- 1.0 vs. 4.3 +/- 0.8 mU/L, p = .02) and IGFBP-1 levels were lower (19.7 +/- 4.6 vs. 43.2 +/- 2.7 mg/L, p = .004) in CFS patients compared with controls.

This study provides preliminary data abnormalities of the GH-IGF axis in CFS. It is not apparent whether these changes are components of a primary pathological process or are acquired secondary to behavioral aspects of CFS such as reduced physical activity.

 

Source: Allain TJ, Bearn JA, Coskeran P, Jones J, Checkley A, Butler J, Wessely S, Miell JP. Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome. Biol Psychiatry. 1997 Mar 1;41(5):567-73. http://www.ncbi.nlm.nih.gov/pubmed/9046989

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214

 

 

Chronic fatigue syndrome: influence of histamine, hormones and electrolytes

Abstract:

The chronic fatigue syndrome is poorly understood. We believe the underlying causes in many atopics and women are a persistent infection and hypersensitivity to the immune-suppressive effects of histamine and certain pathogens.

We believe much of the symptomatology can be explained by all four types of hypersensitivity (Gell and Coombs classification) in reaction to a pathogen, electrolyte disturbances which include sometimes permanent changes in cell membranes’ ability to pass electrolytes, sometimes permanent biochemical changes in mitochondrial function, and disturbances of insulin and T3-thyroid hormone functions. We also explain in detail what ‘fatigue’ means for these patients. We present evidence from the medical literature for the plausibility of our hypotheses.

 

Source: Dechene L. Chronic fatigue syndrome: influence of histamine, hormones and electrolytes. Med Hypotheses. 1993 Jan;40(1):55-60. http://www.ncbi.nlm.nih.gov/pubmed/8455468