Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; alpha-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p < 0.05). TEAC and the cytokine IL-8 increased immediately after the race (p < 0.05). Plasma TNF-alpha remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-alpha response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components.
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PMID:Immune alterations, lipid peroxidation, and muscle damage following a hill race. 1598 88

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are dysregulated in the syndrome. Therapies directed against these cytokines may be of potential importance in the management of fibromyalgia.
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PMID:Is there a role for cytokine based therapies in fibromyalgia. 1645 20

It has been suggested that dental abnormalities lead to temporomandibular joint inflammation and pain that may be mitigated by regular dental care. There is considerable literature on the pathophysiology of equine joint disease including studies on cytokine profiles in diseased appendicular joints. This study examined the effects of age and dental malocclusions summarized as a dental pathology score on equine temporomandibular joint cytokine (IL-1, IL-6, IL-8, TNF alpha and TGF-beta1, -beta2, -beta3) concentrations. TGF-beta3 was not detected in any joint sample. IL-1, IL-6 and TNF alpha were not influenced by age. Foals had significantly lower concentrations of lL-8 and TGF-beta1, and higher levels of TGF-beta2 compared with older horses. Age did not effect cytokine concentration in older horses although there was a trend towards increasing 1L-8 with age. The dental pathology score increased with age in mature horses, however there was no effect of dental pathology score on cytokine concentration. There was no effect of incisor eruption, and presence or number of periodontal lesions on temporomandibular joint cytokine concentration. Our findings indicate that age but not dental pathology affected temporomandibular joint proinflammatory cytokine concentration in this population of horses.
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PMID:Temporomandibular joint cytokine profiles in the horse. 1687 60

Although inflammation has long been known as a localized protective reaction of tissue to irritation, injury, or infection, characterized by pain, redness, swelling, and sometimes loss of function, there has been a new realization about its role in a wide variety of diseases, including cancer. While acute inflammation is a part of the defense response, chronic inflammation can lead to cancer, diabetes, cardiovascular, pulmonary, and neurological diseases. Several pro-inflammatory gene products have been identified that mediate a critical role in suppression of apoptosis, proliferation, angiogenesis, invasion, and metastasis. Among these gene products are TNF and members of its superfamily, IL-1alpha, IL-1beta, IL-6, IL-8, IL-18, chemokines, MMP-9, VEGF, COX-2, and 5-LOX. The expression of all these genes are mainly regulated by the transcription factor NF-kappaB, which is constitutively active in most tumors and is induced by carcinogens (such as cigarette smoke), tumor promoters, carcinogenic viral proteins (HIV-tat, HIV-nef, HIV-vpr, KHSV, EBV-LMP1, HTLV1-tax, HPV, HCV, and HBV), chemotherapeutic agents, and gamma-irradiation. These observations imply that anti-inflammatory agents that suppress NF-kappaB or NF-kappaB-regulated products should have a potential in both the prevention and treatment of cancer. The current review describes in detail the critical link between inflammation and cancer.
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PMID:Inflammation and cancer: how hot is the link? 1688 56

Cytokines have been detected by ELISA in a variety of body fluids. Recycling immunoaffinity chromatography (RIC) coupled with laser-induced fluorescence detection is a highly sensitive and specific method, which allows simultaneous measurements of many analytes in small volumes of biological fluids. This method has been applied to plasma, cervical secretions and other body fluids, but has not previously been applied to sweat. The aim of this study was to validate the RIC methodology in sweat for measurements of IL-1alpha, IL-1beta, IL-6, TNF-alpha, IL-8 and TGF-beta. Two sweat patches were applied for 24 h on the torso, and blood was collected at one time point during this period in nine healthy women. Cytokines were measured in paired samples of plasma and sweat. Cytokines were detected in sweat in similar concentrations to plasma. Linear regression analysis confirmed that sweat levels of these cytokines accounted for a large percentages of variance in plasma levels: IL-1alpha (R2 = 0.70, p = 0.005), IL-1beta (R2 = 0.79, p = 0.003), IL-6 (R2 = 0.52, p = 0.03), TNF-alpha (R2 = 0.95, p < 0.0001), IL-8 (R2 = 0.81, p = 0.001) and TGF-beta (R2 = 0.94, p = 0.0003). These findings indicate that cytokine levels measured in sweat are informative of circulating levels and that sweat patches combined with RIC represents a viable non-invasive method to measure cytokines in ambulatory settings over time. This method is unobtrusive and requires minimal active compliance on the part of the subjects being studied, without pain or stress. This approach can open a new generation of studies to address the effects of environmental factors on immune responses in a wide range of different settings.
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PMID:Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study. 1694 79

The authors analyzed the case of a patient with a non-cemented hip prosthesis with a ceramic-ceramic coupling. As a consequence of trauma the head fractured. Although the patient could feel the joint grinding, there was no pain and he continued daily living activities for nearly six months, which led to marked wearing of the ceramic head. SEM analysis with microprobe showed 'planed' surfaces on the ceramic head, suggesting repeated movements between the fractured components. Inside the cone of the head, signs of TiAlV, which is an alloy of the prosthetic stem, could be seen. Periprosthetic tissues were packed with ceramic wear particles of sizes ranging between 0.2 and 10 microns, according to the harvest site. Metal and mixed particles were also found. IL1, IL6, IL8 and IL10 assays in the synovial liquid confirmed the inflammatory state and a modest induction of bone resorption, which was less than that observed in patients with loosened metal-polyethylene couplings. The humoral picture was compatible with the radiological aspect, which did not show marked signs of bone resorption. In revision surgery both ceramic components were replaced by a metal head and polyethylene liner. The clinical outcome after 12 months was very good.
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PMID:A case report of fracture of ceramic head in total hip arthroplasty: histological and biochemical features of perimplant tissues. 1696 58

It has been suggested that dysregulation of immune-to-brain communication plays a role in the biopsychological process underlying medically unexplained symptoms (MUS). Immune and non-immune stressors can both be involved in the activation of the central sickness-behavioural-system leading to complaints like malaise, pain and fatigue. We hypothesized increased pro-inflammatory and/or reduced anti-inflammatory cytokine activity to exist in MUS patients. Twenty-seven participants (4 male; 23 female) with heterogeneous MUS were compared with 27 healthy controls (6 male; 21 females). Blood samples were analysed for leukocyte subset cell counts, in vitro T-cell mitogen-stimulated cytokine production (IL-2, IL-4, IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) and in vitro monocyte cytokine release (IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha) in response to increasing concentrations of LPS. No significant group differences were found for any of the cytokines measured. One unexpected exception was an elevation in the number of circulating B and NK-cells in participants high on MUS. Nonetheless, no support was found for the hypothesized immunological dysregulation in peripheral blood leukocyte function of MUS patients.
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PMID:Heterogeneous medically unexplained symptoms and immune function. 1755 64

The neurokinin 1 receptor (NK1R), a G protein-coupled receptor involved in diverse functions including pain and inflammation, has two putative N-linked glycosylation sites, Asn-14 and Asn-18. We studied the role of N-linked glycosylation in the functioning of the NK1R by constructing three receptor mutants: two single mutants (Asn --> Gln-14 and Asn --> Gln-18) and a double mutant, lacking both glycosylation sites. Using a lentiviral transfection system, the mutants were stably transfected into NCM 460 cells, a nontransformed human colonic epithelial cell line. We observed that the magnitude of glycosylation as estimated by changes in gel migration depends on the number of glycosylation sites available, with the wild-type receptor containing the greatest amount of glycosylation. All mutant receptors were able to bind to substance P and neurokinin A ligand with similar affinities; however, the double mutant, nonglycosylated NK1R showed only half the B(max) of the wild-type NK1R. In terms of receptor function, the ablation of both N-linked glycosylation sites did not have a profound effect on the receptors' abilities to activate the MAP kinase families (p42/p44, JNK, and p38), but did affect SP-induced IL-8 secretion. All mutants were able to internalize, but the kinetics of internalization of the double mutant receptor was more rapid, when compared with wild-type NK1R. Therefore, glycosylation of NK1R may stabilize the receptor in the plasma membrane. These results contribute to the ongoing elucidation of the role of glycosylation in G protein-coupled receptors and the study of the neurokinin receptors in particular.
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PMID:Functional consequences of alteration of N-linked glycosylation sites on the neurokinin 1 receptor. 1756 89

The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels.APA levels were determined on serum samples by an indirect ELISA kit that detects IgG APA. Cytokines (IL-1, IL-6, IL-8, IL-10 and TNFalpha) were measured by ELISA in plasma. The impact of FM on the quality of life was estimated using the Fibromyalgia Impact Questionnaire, while pain severity was evaluated using a visual analogic scale. Patients were also characterized by the presence of tiredness, stiffness, nonrestorative sleep, anxiety, depression, tension headache, irritable bowel syndrome, temporomandibular dysfunction and Raynaud's phenomena. Using a cut-off value of 30 U, APA-positive values were detected in 60 FM patients (21.05%) and in 15 healthy control individuals (15.00%) without significant differences among their levels or the percentage of seropositivity. FM patients with moderate and severe symptoms had slightly higher APA levels with respect to patients with mild symptoms. APA-seropositive patients exhibited significant correlations between APA levels and the Fibromyalgia Impact Questionnaire estimate (P = 0.042), tiredness (P = 0.003) and IL-1 levels (P = 0.0072). In conclusion, APA cannot be considered a marker of disease in Italian FM patients. The presence of APA, however, might permit the identification of a subset of FM patients with more severe symptoms and of patients who may respond differently to different therapeutic strategies.
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PMID:Antipolymer antibody in Italian fibromyalgic patients. 1782 28


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