Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.
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PMID:Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. 778 Jan 42

Thirty-two patients suffering from migraine without aura were assessed during in interictal period to evaluate the contribution of cytokines to the pathophysiology of migraine. To this end, plasma levels of IFN-gamma, IL-4, IL-5, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) techniques. Plasma levels of both IFN-gamma and IL-10 were not increased in the patients and did not differ significantly from healthy controls. Of interest, we observed a strong increase of IL-5 levels in 84.3% as well as increased IL-4 levels in 37.5% of patients with migraine without aura. These results suggests a preferential enhancement of some Th2-type cytokines, and may support the growing arguments of an immunoallergic mechanism in the pathophysiology of migraine.
Headache 1998 Jun
PMID:Cytokines and migraine: increase of IL-5 and IL-4 plasma levels. 966 52

In the present study, 23 patients with migraine without aura were monitored during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma were measured by enzyme-linked immunosorbent assay techniques. Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels were undetectable in all patients. After treatment with sumatriptan, 10 patients showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5 plasma levels. Although these findings are derived from a limited number of patients, the apparent return to the IL-4 and IL-5 cytokine profile observed during the interictal period leads us to speculate that a preferential enhancement of TH2-type cytokine production may contribute to the pathogenesis of migraine.
Headache 2001 Sep
PMID:Immunological aspects in migraine: increase of IL-10 plasma levels during attack. 1157 99

We report two cases of non-herpetic acute limbic encephalitis (NHALE) which showed elevation of interleukin (IL)-6 in the cerebrospinal fluid (CSF). [Case 1] The patient was a 25-year-old woman who was admitted to another hospital because of fever and severe headache, following common cold. After the admission, she developed severe disturbance of consciousness and suffered from generalized convulsions, and was then transferred to our hospital. The CSF examination revealed neither pleocytosis nor elevation of total protein. Her consciousness improved by intravenous administration of high-dose methylprednisolone, but mild retrograde amnesia and symptomatic epilepsy remained as sequelae. [Case 2] The patient was a 58-year-old man who was admitted to our hospital because of fever, severe headache, and mild disturbance of consciousness, following common cold. After the admission, he exhibited marked psychiatric symptoms and severe amnestic syndrome. The CSF examination revealed mild lymphocytic pleocytosis and mild elevation of total protein. His clinical symptoms improved markedly by intravenous administration of high-dose methylprednisolone, but mild retrograde amnesia and personality changes remained. Cranial MRI showed reversible high signal intensity lesions in bilateral hippocampi and amygdaloid bodies on diffusion weighted images (DWI) in both cases. No laboratory findings suggesting herpes simplex virus infection or malignancy were detected in either case. In the CSF analysis of cytokines including IL-1 beta, IL-2, IL-6, IL-10, tumor necrosis factor alpha, and interferony gamma, only IL-6 was elevated in both cases. We recognized four clinical features in both cases as follows: 1. the episode of preceding infection such as common cold, 2. appearance of reversible high signal intensity lesions in bilateral hippocampi and amygdaloid bodies on DWI, 3. elevation of only IL-6 in CSF, and 4. marked neurological improvement by intravenous administration of high-dose methylprednisolone. We speculate that the immune reaction of the host might play some significant roles in the pathogenesis of NHALE, based on these four clinical features.
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PMID:[The analysis of cytokines in cerebrospinal fluid (CSF) in two cases of non-herpetic acute limbic encephalitis (NHALE)]. 1288 25

Migraine without aura (MO) and migraine with aura (MA) are disorders involving multiple environmental and genetic factors. The A/G polymorphism located within exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA-4) is associated with several HLA-associated multifactorial diseases. The CTLA-4 family shows a negative control on T-cell proliferation and cytokine production (TNF-alpha and IL-10). In the present study we investigated the contribution of the candidate gene CTLA-4 in migraine pathophysiology. Included in the study were 96 MO and 39 MA migraine patients and 106 healthy individuals as control group. The results showed no statistical difference of allele frequencies between patient group and control group. These results would indicate no association between MA and MO migraine and CTLA-4 polymorphism, excluding any possible role of the CTLA-4 gene as a genetic factor determining susceptibility to migraine.
J Headache Pain 2005 Sep
PMID:Cytotoxic T lymphocyte antigen 4 polymorphism 49 (A>G) and migraine. 1636 60

In order to predict the clinical benefit of interferon-beta (IFN-beta) to patients with multiple sclerosis (MS), the following markers were investigated; (1) chronological change of cytokines (IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta) after administration of IFN-beta, (2) untoward effects of IFN-beta such as headache and arthralgia, (3) backgrounds of the patients such as age and relapse rate, (4) efficacy of IFN-beta therapy assessed by the change of relapse rate and progression of disability. Chronological blood sampling was performed 0, 10, and 24 h after injection of IFN-beta. The increase of serum IL-6 level in response to IFN-beta administration was associated with headache, arthralgia, relapse rate before treatment, and disability score at the initiation of the therapy. Significant association of change of serum TNF-alpha with age and headache was also observed. The important finding in this study was that patients with a transient increase in IL-6 in response to IFN-beta showed a slow disease progression. This result suggests that this transient increase in the serum IL-6 predicts favorable response to IFN-beta treatment.
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PMID:Beneficial effect of interferon-beta treatment in patients with multiple sclerosis is associated with transient increase in serum IL-6 level in response to interferon-beta injection. 1716 13

Headache and/or migraine, a common problem in pediatrics and internal medicine, affect about 5% to 10% children and adolescents, and nearly 30% of middle-aged women. Headache is also one of the most common clinical manifestations of acquired Toxoplasma gondii infection of the central nervous system (CNS) in immunosuppressed subjects. We present 11 apparently nonhuman immunodeficiency virus-infected children aged 7 to 17 years (8 girls, 3 boys) and 1 adult woman with recurrent severe headaches in whom latent chronic CNS T. gondii infection not manifested by enlarged peripheral lymph nodes typical for toxoplasmosis, was found. In 7 patients, the mean serum IgG Toxoplasma antibodies concentration was 189 +/- 85 (SD) IU/mL (range 89 to 300 IU/mL), and in 5 other subjects, the indirect fluorescent antibody test titer ranged from 1:40 to 1:5120 IU/mL (n= <1:10 IU/mL). Some of the patients suffered also from atopic dermatitis (AD) and were exposed to cat and/or other pet allergens, associated with an increased IL-4 and decreased IFN-gamma production. These cytokine irregularities caused limited control of cerebral toxoplasmosis probably because IL-4 down-regulated both the production of IFN-gamma and its activity, and stimulated production of a low NO-producing population of monocytes, which allowed cysts rupture, increased parasite multiplication and finally reactivation of T. gondii infection. The immune studies performed in 4 subjects showed a decreased percentage of T lymphocytes, increased total number of lymphocytes B and serum IgM concentration, and impaired phagocytosis. In addition, few of them had also urinary tract diseases known to produce IL-6 that can mediate immunosuppressive functions, involving induction of the anti-inflammatory cytokine IL-10. These disturbances probably resulted from the host protective immune reactions associated with the chronic latent CNS T. gondii infection/inflammation. This is consistent with significantly lower enzyme indoleamine 2,3-dioxygenase (IDO) activity reported in atopic than in nonatopic individuals, and an important role that IDO and tryptophan degradation pathways plays in both, the host resistance to T. gondii infection and its reactivation. Analysis of literature information on the subjects with different types of headaches caused by foods, medications, and other substances, may suggest that their clinical symptoms and changes in laboratory data result at least in part from interference of these factors with dietary tryptophan biotransformation pathways. Several of these agents caused headache attacks through enhancing NO production via the conversion of arginine to citrulline and NO by the inducible nitric oxide synthase enzyme, which results in the high-output pathway of NO synthesis. This increased production of NO is, however, quickly down-regulated by NO itself because this biomolecule can directly inactivate NOS, may inhibit Ia expression on IFN-gamma-activated macrophages, which would limit antigen-presenting capability, and block T-cell proliferation, thus decreasing the antitoxoplasmatic activity. Moreover, NO inhibits IDO activity, thereby suppressing kynurenine formation, and at least one member of the kynurenine pathway, 3-hydroxyanthranilic acid, has been shown to inhibit NOS enzyme activity, the expression of NOS mRNA, and activation of the inflammatory transcription factor, nuclear factor-kB. In addition, the anti-inflammatory cytokines IL-4 and IL-10, TGF-beta, and a cytokine known as macrophage deactivating factor, have been shown to directly modulate NO production, sometimes expressing synergistic activity. On the other hand, IL-4 and TGF-beta can suppress IDO activity in some cells, for example human monocytes and fibroblasts, which is consistent with metabolic pathways controlled by IDO being a significant contributor to the proinflammatory system. Also, it seems that idiopathic intracranial hypertension, pseudotumor cerebri, and aseptic meningitis, induced by various factors, may result from their interference with IDO and inducible nitric oxide synthase activities, endogenous NO level, and cytokine irregularities which finally affect former T. gondii status 2mo in the brain. All these biochemical disturbances caused by the CNS T. gondii infection/inflammation may also be responsible for the relationship found between neurologic symptoms, such as headache, vertigo, and syncope observed in apparently immunocompetent children and adolescents, and physical and psychiatric symptoms in adulthood. We therefore believe that tests for T. gondii should be performed obligatorily in apparently immunocompetent patients with different types of headaches, even if they have no enlarged peripheral lymph nodes. This may help to avoid overlooking this treatable cause of the CNS disease, markedly reduce costs of hospitalization, diagnosis and treatment, and eventually prevent developing serious neurologic and psychiatric disorders.
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PMID:Recurrent headache as the main symptom of acquired cerebral toxoplasmosis in nonhuman immunodeficiency virus-infected subjects with no lymphadenopathy: the parasite may be responsible for the neurogenic inflammation postulated as a cause of different types of headaches. 1730 77

Dramatic relief of pain and life-altering changes in quality of life in some patients treated with immunomodulators such as thalidomide compel us to look more closely at unconventional mechanisms that may be involved in propagation of persistent pain. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 are the cytokines with the most evidence in pain modulation. TNF-alpha and IL-1beta seem to initiate neuropathic pain, IL-6 maintains such pain, and IL-10 inhibits this persistent pain. Thalidomide was found to be effective in animal models by inhibiting TNF-alpha production. Several case reports and case series in humans have demonstrated mixed results, with some patients having dramatic responses, especially in chronic intractable conditions such as complex regional pain syndrome. Thalidomide may be an alternative for some patients with intractable pain. However, use of thalidomide is limited by its neurotoxic and teratogenic effects. Newer analogues may significantly improve the risk/benefit of using such immunomodulators.
Curr Pain Headache Rep 2007 Apr
PMID:Does thalidomide have an analgesic effect? Current status and future directions. 1736 89

Migraine is a common disorder, characterized by recurrent episodes of headache and associated symptoms. The full pathophysiology of migraine is incompletely delineated. Current theories suggest that it is a neurovascular disorder involving cortical depression, neurogenic inflammation and vasodilation. Various neuropeptides and cytokines have been implicated in the pathophysiology of migraine including calcitonin gene-related peptide, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha. There is evidence demonstrating an association between migraine and processes associated with inflammation, atherosclerosis, immunity and insulin sensitivity. Similarly, adiponectin, an adipocytokine secreted by adipose tissue, has protective roles against the development of insulin resistance, dyslipidaemia and atherosclerosis and exhibits anti-inflammatory properties. The anti-inflammatory activities of adiponectin include inhibition of IL-6 and TNF-induced IL-8 formation, as well as induction of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist. Adiponectin levels are also inversely correlated with C-reactive protein (CRP), TNF-alpha and IL-6 levels. Likewise, recent studies have shown a possible correlation between CRP, TNF-alpha and IL-6 and migraine attacks. In addition, insulin sensitivity is impaired in migraine and obesity is a risk factor for the transformation from episodic to chronic migraine. In this review we discuss the basic science of adiponectin and its potential connection to the pathophysiology of migraine. Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.
Cephalalgia 2007 May
PMID:Migraine and adiponectin: is there a connection? 1744 81

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-beta1 (TGF-beta1)] were included. There were significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.
Cephalalgia 2009 Mar
PMID:Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache. 1917 74


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