Tag: sex differences

A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome

Abstract:

BACKGROUND: Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female).

METHODS: Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group.

RESULTS: Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects.

CONCLUSIONS: Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.

 

Source: Smylie AL, Broderick G, Fernandes H, Razdan S, Barnes Z, Collado F, Sol C, Fletcher MA, Klimas N. A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol. 2013 Jun 25;14:29. doi: 10.1186/1471-2172-14-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698072/ (Full article)

 

Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndromepatients with and without comorbid fibromyalgia

Abstract:

BACKGROUND: Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls.

METHODS: Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of L-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined.

RESULTS: Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups.

CONCLUSIONS: These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM.

 

Source: Weaver SA, Janal MN, Aktan N, Ottenweller JE, Natelson BH. Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndrome patients with and without comorbid fibromyalgia. J Womens Health (Larchmt). 2010 May;19(5):951-8. doi: 10.1089/jwh.2009.1697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875960/ (Full article)

 

Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls

Abstract:

CONTEXT: A substantial body of research on the pathophysiology of chronic fatigue syndrome (CFS) has focused on hypothalamic-pituitary-adrenal axis dysregulation. The cortisol awakening response has received particular attention as a marker of hypothalamic-pituitary-adrenal axis dysregulation.

OBJECTIVE: The objective of the current study was to evaluate morning salivary cortisol profiles in persons with CFS and well controls identified from the general population.

DESIGN AND SETTING: We conducted a case-control study at an outpatient research clinic.

CASES AND OTHER PARTICIPANTS: We screened a sample of 19,381 residents of Georgia and identified those with CFS and a matched sample of well controls. Seventy-five medication-free CFS cases and 110 medication-free well controls provided complete sets of saliva samples.

MAIN OUTCOME MEASURES: We assessed free cortisol concentrations in saliva collected on a regular workday immediately upon awakening and 30 and 60 min after awakening.

RESULTS: There was a significant interaction effect, indicating different profiles of cortisol concentrations over time between groups, with the CFS group showing an attenuated morning cortisol profile. Notably, we observed a sex difference in this effect. Women with CFS exhibited significantly attenuated morning cortisol profiles compared with well women. In contrast, cortisol profiles were similar in men with CFS and male controls.

CONCLUSIONS: CFS was associated with an attenuated morning cortisol response, but the effect was limited to women. Our results suggest that a sex difference in hypocortisolism may contribute to increased risk of CFS in women.

 

Source: Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. J Clin Endocrinol Metab. 2008 Mar;93(3):703-9. Epub 2007 Dec 26. https://www.ncbi.nlm.nih.gov/pubmed/18160468

 

The epidemiology of chronic fatigue in the Swedish Twin Registry

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity.

METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS.

FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender.

INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

 

Source: Evengård B, Jacks A, Pedersen NL, Sullivan PF. The epidemiology of chronic fatigue in the Swedish Twin Registry. Psychol Med. 2005 Sep;35(9):1317-26. http://www.ncbi.nlm.nih.gov/pubmed/16168154

 

Gene expression profiling in the chronic fatigue syndrome

Fatigue is a symptom found in many conditions of disease and illness. Although, unfrequently recognized by the medical profession, it is often of major importance for the patients. Chronic fatigue was reported by 5.9% of the Swedish population in a large telephone-based interview with 31 406 individuals in the Swedish twin registry (STR) [1]. The fatigue had lasted for more than 6 months and caused impairment, e.g. >25% reduction of working capacity. When at least four of eight criteria included in the current definition of chronic fatigue syndrome (CFS) [2] was added 2.4% reported that they suffered from a CFS-like illness.

This costly condition is still an intriguing issue for researchers and clinicians, and ambiguities in the definition have recently been focused upon [3, 4]. An empirical test of the definition was performed with data from the STR where five subgroups were identified: ‘CFS-like’, ‘residual’, ‘rheumatic’, ‘depressive’ and ‘acute physical syndrome’ [5].

We wanted to identify genes in peripheral blood mononuclear cells (PBMCs), which may play an important role in the pathogenesis and diagnostics of CFS, using microarray technology. PBMCs can serve as indicators of illness processes occurring in different parts of the human body. Patients with CFS from a clinic of infectious diseases at a university hospital were stratified according to the STR study findings [5] to sex, illness classification (ICD-10), illness onset type, illness duration and number of symptoms (Table 1).

You can read the rest of this article here: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01548.x/full

 

Source: Gräns H, Nilsson P, Evengard B. Gene expression profiling in the chronic fatigue syndrome. J Intern Med. 2005 Oct;258(4):388-90. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01548.x/full (Full article)

 

Study of immune alterations in patients with chronic fatigue syndrome with different etiologies

Abstract:

The Chronic Fatigue Syndrome (CFS) is characterized by symptoms lasting for at least six months and accompanied by disabling fatigue. The etiology of CFS is still unclear.

At the National Center for Study of the Infectious Diseases Department of the Chieti University some immune investigations were performed with the purpose of detecting markers of the disease. CD4+, CD8+, NK CD56+ and B CD19+ lymphocytes were studied in 92 male and 47 female patients and in 36 control subjects. CFS patients were divided in three groups with a post-infectious onset (PI-CFS), an non post-infectious onset (NPI-CFS) and a non post-infectious onset with associated infections (NPI-CFS + AI).

Both CD4+ and CD8+ lymphocytes were reduced in the CFS patients. However, the CD4+/CD8+ ratio was increased in the CFS patients without difference between males and females. CD56+ cells of CFS patients were also reduced. In particular, blood CD56+ cells counts were significantly higher in PI-CFS patients than in the NPI-CFS subjects. These data confirm our preliminary results suggesting a key-role of a dysfunction of the immune system as a precipitating and-or perpetuating factor of the syndrome.

 

Source: Racciatti D, Dalessandro M, Delle Donne L, Falasca K, Zingariello P, Paganelli R, Pizzigallo E, Vecchiet J. Study of immune alterations in patients with chronic fatigue syndrome with different etiologies. Int J Immunopathol Pharmacol. 2004 May-Aug;17(2 Suppl):57-62. http://www.ncbi.nlm.nih.gov/pubmed/15345193

 

Gender differences in host defense mechanisms

Abstract:

Extensive studies in both humans and animals have shown that females express enhanced levels of immunoreactivity compared to males. Whereas this provides females with increased resistance to many types of infection, it also makes them more susceptible to autoimmune diseases. This review will focus on gender-related differences in non-specific host defense mechanisms with a particular emphasis on monocyte/macrophage function and a primary product of monocytes: interleukin-1 (IL-1). Immunomodulatory cytokines such as IL-1 are influenced by gender-sensitive hormones, and reciprocally, these cytokines influence gender-specific hormones and tissues. Patients with chronic fatigue syndrome (CFS) are predominantly women, therefore it may be useful to look toward gender-specific differences in immune function to find a key for this poorly understood syndrome.

 

Source: Cannon JG, St Pierre BA. Gender differences in host defense mechanisms. J Psychiatr Res. 1997 Jan-Feb;31(1):99-113. http://www.ncbi.nlm.nih.gov/pubmed/9201652

 

Gender differences in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine whether there are differences between men and women patients who have chronic fatigue syndrome (CFS) and, if so, to ascertain whether a gender-related pattern exists.

DESIGN: A descriptive study of demographic, clinical, and psychosocial measures, the results of which were prospectively collected for patients who had CFS.

SETTING: A university-based referral clinic devoted to the evaluation and management of chronic fatigue.

PATIENTS: 348 CFS patients who had undergone complete medical evaluations.

MEASURES: Clinical variables included symptoms, physical examination findings, and laboratory results. Psychosocial assessment consisted of a structured psychiatric interview, the Medical Outcomes Study Short-form General Health Survey to assess functional status, the General Health Questionnaire to ascertain psychological distress, the Multidimensional Health Locus of Control, and measures of attribution, social support, and coping.

MAIN RESULTS: Overall, few gender-related differences were identified. Women had a higher frequency of tender or enlarged lymph nodes (60% versus 33%, p < or = 0.01) and fibromyalgia (36% versus 12%, p < or = 0.001) and lower scores on the physical functioning subscale of the Medical Outcomes Study Short-form General Health Survey (37.6 versus 52.2, p < 0.01); men more often had pharyngeal inflammation (42% versus 22%, p < or = 0.001) and reported a higher lifetime prevalence of alcoholism (20% versus 9%, p < or = 0.01).

CONCLUSIONS: In general, demographic, clinical, and psychosocial factors do not distinguish men from women CFS patients.

 

Source: Buchwald D, Pearlman T, Kith P, Schmaling K. Gender differences in patients with chronic fatigue syndrome. J Gen Intern Med. 1994 Jul;9(7):397-401. http://www.ncbi.nlm.nih.gov/pubmed/7931750

 

Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls

Abstract:

AIMS: To investigate the possibility of a correlation between the percentage of nondiscocytic erythrocytes and muscle fatiguability in subjects with the symptom of chronic tiredness.

METHODS: Sixty nine volunteers suffering from persisting or intermittent tiredness and 72 healthy controls provided 3-drop samples of venous blood for red cell shape analysis before and after inducing fatigue in the trigger finger muscles by repeatedly pulling the trigger of an antique revolver. Elapsed time and the number of pulls were recorded. A work index was calculated from the number of trigger pulls divided by the time in seconds then multiplied by the number of trigger pulls.

RESULTS: Subjects with tiredness had fewer discoid cells (males 62.5% vs 69.2%, p = 0.029; females 65.8% vs 71.8%, p = 0.002) than controls. They also had fewer trigger pulls (males 62.3 vs 84.0, p = 0.003; females 29.5 vs 36.8, p = 0.042) and lower “work indices” (males 75.6 vs 104.7, p = 0.001; females 26.1 vs 39.6, p = 0.001) than controls at the first trigger pulling. After 5 minutes rest the number of trigger pulls for males was fewer than the controls (56.0 vs 64.2) but the difference was not significant, but the female values (24.3 vs 33.2) were significantly different (p = 0.008). Work indices for both sexes were significantly different from controls (males p = 0.020, females p = 0.001).

CONCLUSIONS: The association of increased nondiscocytes and impaired muscle function could indicate a cause and effect relationship. This would be in agreement with the physiological concept of fatigue as a consequence of inadequate oxygen delivery.

 

Source: Simpson LO, Murdoch JC, Herbison GP. Red cell shape changes following trigger finger fatigue in subjects with chronic tiredness and healthy controls. N Z Med J. 1993 Mar 24;106(952):104-7. http://www.ncbi.nlm.nih.gov/pubmed/8474717