Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031927 (cytokine)
 144,509 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The back pain syndrome which accompanies involutional osteoporosis presents a marked heterogeneity. Acute pain may be due to vertebral fractures, whereas chronic pain may eventually accompany established osteoporosis in which clinical and instrumental evidence are present. Back pain is the consequence of the mechanical (internal or external pressure) or chemical stimulation of pain receptors present in bone tissue, along the vessels, in cartilage, joints, disk, ligaments, and also in soft tissue and muscle (with secondary antalgic contracture). The compression of spinal nerves may contribute to the pain as well. An evident alteration of mood is usually present and represents an important element in the syndrome. This phenomenon interferes with the evolution of pain, in particular as regards its intensity. Besides scales for the evaluation of pain and inability, it is possible to check objective data by means of particular algometers (not easy to employ) or by electromyographic measurements of antalgic secondary contracture of spinal muscle. Gait examination (basography) of patients with painful hip prosthesis may provide objective evaluation regarding specific antalgic activity on bone of drugs. Usually the effective drugs for osteoporosis possess antalgic properties as well, with different mechanisms of action. Three drugs with evident activity are taken into consideration: calcitonin, ipriflavon, aminobutane-bisphosphonate (alendronate). Though each of them possesses some particular activity, the main mechanism of action is dependent on their effect on the local microenvironment, particularly at the level of bone tissue (calcium, cytokine and prostaglandin local concentration), on the modulation of osteoclast activity. In particular alendronate (intermittently administered intravenously) exerts the most evident antalgic activity. Subjective chronic back pain relief is accompanied by (secondary) reduction of antalgic contracture at vertebral muscle level. The activity of the substance against the painful hip prosthesis (documented by basographic gait recording) leads us to conclude that the substance really exerts a direct antalgic action at the level of bone tissue.
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PMID:[Treatment experience with chronic spinal pain in involutional osteoporosis]. 129 92

Disease patterns in RA vary between the sexes; the condition is more commonly seen in women, who exhibit a more aggressive disease and a poorer long-term outcome. Men, however, are more likely than women to die from extra-articular complications of rheumatoid disease. This chapter discusses the outcome and mortality studies that substantiate these conclusions and then examines the possible mechanisms that may account for them, including the HLA system, seropositivity, compliance, response to therapy and pain threshold. In particular, sex and sex hormones emerge as independent risk factors in rheumatoid disease. The epidemiological evidence points towards a peak age of onset of RA at the time of the menopause in women and towards later in life in men. Premenopausal women may fare better than postmenopausal women with RA. The possible protective effects of the oral contraceptive pill and the dramatic amelioration with pregnancy are well documented. In vivo and in vitro studies have demonstrated that sex hormones interfere with a number of the putative processes involved in the pathogenesis of RA, including immunoregulation, interaction with inflammatory mediators and the cytokine system, and direct effects on cartilage itself. All these observations point towards the importance of gonadal hormones. However, trials on the potential therapeutic use of sex hormones in RA are limited and, as yet, disappointing. Further work is necessary to determine whether the roles of sex hormones are as central protagonists or just supporting cast in the complex arena of rheumatoid disease.
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PMID:The effects of gender and sex hormones on outcome in rheumatoid arthritis. 156 36

Seventy-five consecutive patients undergoing laparoscopy for chronic pelvic pain and/or infertility were studied to test whether beta-endorphin concentrations in peripheral mononuclear cells differed according to the presence or absence of endometriosis. Endometriosis was diagnosed in 45 subjects (minimal in 24, mild in 11, moderate in four, and severe in six). Twenty-eight women (62%) with endometriosis and ten (33%) without the disease reported moderate or severe pelvic pain. beta-Endorphin levels were lower in the endometriosis group than in the controls (16.6 +/- 11.2 versus 21.9 +/- 10.5 pg/10(6) cells; P less than .01). This decrease was attributable to reduced beta-endorphin concentrations in the endometriosis patients with moderate or severe pain compared with symptomatic controls (15.5 +/- 10.0 versus 26.3 +/- 7.0 pg/10(6) cells; P less than .01). A significant difference was also found in relation to the cycle phase: The opioid concentration was reduced in the luteal phase in the endometriosis group compared with controls (14.4 +/- 8.4 versus 23.8 +/- 7.5 pg/10(6) cells; P less than .01), but no differences were demonstrated in the follicular and periovulatory phases. beta-Endorphin is capable of modulating the immune response and can be considered as a classical cytokine. Low beta-endorphin production during the luteal phase may have implications in the development and/or maintenance of endometriosis.
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PMID:Mononuclear cell beta-endorphin concentration in women with and without endometriosis. 156 59

To evaluate systemic cytokine and hypothalamic-pituitary-adrenal axis responses in migraine, we measured plasma levels of tumour necrosis factor, interleukin-1, adrenocorticotropic hormone, and cortisol, as well as body temperature during and between attacks in 20 migraine patients. We found no evidence of systemic rise of cytokines during migraine attacks. Plasma cortisol and adrenocorticotropic hormone responses were similar to those found to experimentally-induced pain in normal subjects, i.e. elevated cortisol and unchanged adrenocorticotropic hormone levels. Unexpectedly, body temperature tended to be lower during attacks.
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PMID:Plasma interleukin-1, tumour necrosis factor and hypothalamic-pituitary-adrenal axis responses during migraine attacks. 165 Feb 89

Cytokines of rabbit synovial origin were injected into 6 rats under the epineurium of the sciatic nerve. Five controls were injected with similar preparations lacking cytokines. After injection, rats were examined for a period of 7 days. For neurophysiological evaluation the tibial branch of the sciatic nerve was stimulated with supramaximal voltage impulses of constant duration. The responses were recorded at the dorsal root entry zone L1. F-wave latencies were recorded at the distal hind paw after stimulation of the tibial nerve. Filters were set at LF: 20 Hz, HF: 10 kHz. Synovial cytokines caused a significant decrease in amplitude and increase in latencies of the recorded nerve potentials. Our results indicate that interleukin-1, which is a major component of the synovial cytokine preparation, could play an important role in degenerative spine disease through a damaging effect on nerve function. This action would explain why radiculopathy and pain can develop without signs of nerve compression. The results are also relevant to patients suffering from osteoarthritis and rheumatoid arthritis.
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PMID:[The interaction between synovial cytokines and peripheral nerve function: a potential element in the development of radicular syndrome]. 214 30

Bradykinin and its active metabolites, produced by kallikreins at their sites of action, potently elicit a variety of biological effects: hypotension, bronchoconstriction, gut and uterine contraction, epithelial secretion in airway, gut, and exocrine glands, vascular permeability, pain, connective tissue proliferation, cytokine release, and eicosanoid formation. These effects are mediated by at least two broad classes of receptors. The most common is the B2 subtype. The availability of competitive antagonists of B2 receptors has provided powerful tools for the study of bradykinin's actions. The significance of kinins in certain human diseases is being explored by using these agents as potential therapeutic agents. Human clinical trials are under way to test the usefulness of bradykinin receptor antagonists to treat symptoms of the common cold and the pain associated with severe burns. Trials are also being comtemplated for use in treatment of asthma.
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PMID:Antagonists of B2 bradykinin receptors. 254 96

Tissue injury or the presence of foreign material initiates a series of pathophysiological events that may manifest as inflammatory pain. The physicochemical characteristics of the initiating factor trigger the release of a unique range of pain mediators that control the threshold and activation of nociceptors. It has been suggested that many nociceptors associated with inflammatory pain are dormant, and are activated by cyclo-oxygenase metabolites and sympathomimetic amines into a state of hyperalgesia. In this state, pain receptors may be activated by previously ineffective stimuli. The relative contribution of the mediators to the activation process varies with the experimental model or the pathophysiological process involved. The mechanisms that control the activity of the pain receptor are unfolding. Indeed, research has shown a central role for bradykinin (released from plasma) and cytokines (released from tissues and resident cells) in this process. The release of tumour necrosis factor-alpha (TNF-alpha) initiates the release of interleukin-1 and interleukin-8, which in turn liberate cyclo-oxygenase metabolites and sympathomimetic amines, respectively. In some models of inflammatory pain, bradykinin causes hyperalgesia via release of TNF-alpha. Drugs blocking cyclo-oxygenase (aspirin-like drugs), or those antagonising the effects of sympathomimetic amines (beta-blockers), prevent sensitisation of the pain receptors. However, during hyperalgesia only specific types of analgesics are capable of nociceptor downregulation. It is assumed that sensitisation of nociceptors is due to increased concentrations of cAMP/Ca++ in the sensory neurons. The effect of increased cAMP concentrations may be counteracted by stimulation of the arginine/nitric oxide/cGMP pathway. Peripherally acting opiates and dipyrone are examples of analgesics that act via this mechanism. The analgesic effects of glucocorticoids and nimesulide appear to be attributable to inhibition of cytokine release.
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PMID:The role of interleukins and nitric oxide in the mediation of inflammatory pain and its control by peripheral analgesics. 750 42

African sleeping sickness, characterized by a peculiar pain syndrome and prominent neuropsychiatric symptoms, is caused by the parasite Trypanosoma brucei (T.b.). In experimental T.b. infections, a molecule released from the trypanosomes has been isolated that binds to the CD8 molecule of T cells, whereby T cells are activated to secrete interferon gamma. This cytokine binds to the parasites and triggers them to proliferate, establishing a peculiar bidirectional activating signal system. The hypothesis is presented that the molecules involved in these bidirectional signals might also interact with neurons, thus causing brain dysfunctions. Studies on the molecular interactions between parasites and the nervous system in sleeping sickness might reveal basic mechanisms underlying other neuropsychiatric diseases.
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PMID:Trypanosoma brucei and the nervous system. 752 99

Vaso-occlusive pain episodes in sickle cell anemia are hypothesized to be precipitated by adherence of sickle erythrocytes to vascular endothelium in the microcirculation. Febrile episodes, thought to be viral in etiology, are frequently associated with vaso-occlusion; however, a direct link between viral infection and vascular occlusion has not yet been established. Many pathogenic viruses contain double-stranded RNA or replicate through double-stranded RNA intermediates. Double-stranded RNA has been shown to induce vascular cell adhesion molecule-1 (VCAM-1) protein expression on endothelial cells. Recently, a new adhesion pathway has been described between VCAM-1 expressed on cytokine stimulated endothelium and the alpha 4 beta 1 integrin complex expressed on sickle reticulocytes. Based on these observations, the hypothesis was developed that viral infection, through double-stranded RNA intermediates, increases endothelial VCAM-1 expression leading to sickle erythrocyte adhesion to endothelium via an alpha 4 beta 1-VCAM-1--dependent mechanism. In support of this hypothesis, endothelial cells exposed to the synthetic double-stranded RNA poly(I:C) or the RNA virus parainfluenza 1 (Sendai virus) express increased levels of VCAM-1 and support increased sickle erythrocyte adherence under continuous flow at 1.0 dyne/cm2 shear stress as compared with unstimulated endothelium. Blocking antibodies directed against either VCAM-1 on the endothelium or alpha 4 beta 1 on sickle erythrocytes inhibit nearly all of the increased sickle cell adherence caused by poly(I:C) or Sendai virus. These results support the hypothesis that viruses, through double-stranded RNA elements, can induce sickle erythrocyte adherence to endothelium through alpha 4 beta 1-VCAM-1--mediated adhesion and provide a potential link between viral infection and microvascular occlusion precipitating sickle cell pain episodes.
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PMID:Double-stranded RNA induces sickle erythrocyte adherence to endothelium: a potential role for viral infection in vaso-occlusive pain episodes in sickle cell anemia. 753 85

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.
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PMID:Mediation of inflammation by cyclooxygenase-2. 761 Sep 90


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