INT12720

Context Info Confidence 0.70 First Reported 1990 Last Reported 2011 Negated 6 Speculated 3 Reported most in Body Documents 246 Total Number 249 Disease Relevance 195.97 Pain Relevance 72.05

Anatomy Link Frequency macrophages 12 brain 12 joints 7 CSF 3 neutrophils 3 Il1 (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 5847 100.00 cytokine 5454 100.00 chemokine 765 100.00 antagonist 633 100.00 Inflammatory mediators 317 100.00 Inflammatory marker 73 100.00 Central nervous system 1186 99.98 Enkephalin 19 99.98 Root ganglion neuron 1 99.88 Osteoarthritis 594 99.84

Disease Link Frequency Relevance Heat INFLAMMATION 6627 100.00 Fever 284 100.00 Contact Dermatitis 49 99.98 Disease 3667 99.96 Alzheimer's Dementia 1784 99.96 Acquired Immune Deficiency Syndrome Or Hiv Infection 216 99.94 Arthritis 3323 99.92 Cancer 810 99.92 Bronchopulmonary Dysplasia 16 99.88 Osteoarthritis 583 99.84

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Event

Anatomy

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Speculation

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Disease term

In turn, these substances bind kappa-opioid receptors expressed in GM-CSF-activated macrophage-like stromal cells and seem to stimulate IL-1.

Spec (seem) Positive_regulation (stimulate) of IL-1 in macrophage associated with kappa opioid receptor

1) Confidence 0.70 Published 2000 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 11268355 Disease Relevance 0.58 Pain Relevance 0.34

Although barely detectable in the normal brain, IL-1 is dramatically upregulated during neuroinflammation, and also displays peaks of expression in the brain during development, as well as following the induction of long-term potentiation.

Positive_regulation (upregulated) of IL-1 in brain associated with long-term potentiation

2) Confidence 0.69 Published 2009 Journal Brain Behav. Immun. Section Abstract Doc Link 19258032 Disease Relevance 0.35 Pain Relevance 0.09

Treatment with taurine and niacin attenuated the BL-induced increases in proinflammatory cytokines such as IL-1alpha, TNF-alpha, IL-6, and TGF-beta in BALF and lung hydroxyproline content of the mice in BL + TN groups.

Positive_regulation (increases) of IL-1 in lung associated with cytokine

3) Confidence 0.67 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10734156 Disease Relevance 0.29 Pain Relevance 0.21

Reverse transcription-polymerase chain reaction analysis of total RNA from whole lung was performed to assess the induction of TNF-alpha and IL-1 mRNAs as markers of NF-kappaB activation.

Positive_regulation (induction) of IL-1 in lung

4) Confidence 0.67 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10734156 Disease Relevance 0.26 Pain Relevance 0.19

In response to homeostatic threats in mammals, increased IL-1 levels activate the hypothalamo-pituitary-adrenal (HPA) axis and are central to elicitation of sickness behaviors.

Positive_regulation (increased) of IL-1 in pituitary

5) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.59 Pain Relevance 0.32

Experimentally induced elevations of IL-1?

Positive_regulation (elevations) of IL-1

6) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.20 Pain Relevance 0.20

The initial stimulus for elevation of IL-1 in AD is likely the result of exposure of microglia to injured neurons, ?

Positive_regulation (elevation) of IL-1 in neurons associated with alzheimer's dementia

7) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.73 Pain Relevance 0.08

This pattern of expression was further extended to animal models of CNS injury where parenchymal IL-1 mRNA and protein levels are elevated in experimental models of ischemia, excitotoxicity, infection and traumatic brain injury in rodents.

Positive_regulation (elevated) of IL-1 in brain associated with ischemia, injury, central nervous system, brain injury and infection

8) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 1.73 Pain Relevance 0.29

Furthermore, increased IL-1 has been detected in CSF samples in MS, Parkinson's and Creutzfeldt-Jakob disease (CJD) [26-28].

Positive_regulation (increased) of IL-1 in CSF associated with creutzfeldt jakob disease, disease and demyelinating disease

9) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 2.37 Pain Relevance 0.17

Also, injection of lipopolysaccharide (LPS), a potent inducer of IL-1?

Positive_regulation (inducer) of IL-1

10) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.52 Pain Relevance 0.29

IL-1 elevations became closely tied to AD pathogenesis soon after the discovery of prominent neuroinflammation in AD brain.

Positive_regulation (elevations) of IL-1 in brain associated with alzheimer's dementia

11) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 1.58 Pain Relevance 0.31

As highlighted above, IL-1 elevation may potentiate plaque degradation by enhancing microglial activation and phagocytic activity, as well as seeding of peripheral phagocytic cells to areas of plaque deposition [44].

Positive_regulation (elevation) of IL-1 in plaque

12) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.71 Pain Relevance 0.07

By feeding back upon itself, small localized elevations in IL-1 may be sufficient to drive potent neuroinflammatory changes in the brain.

Positive_regulation (elevations) of IL-1 in brain

13) Confidence 0.60 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2335091 Disease Relevance 0.52 Pain Relevance 0.32

Moreover, the result of high circulating TNF and IL-1?

Positive_regulation (circulating) of IL-1

14) Confidence 0.49 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2844385 Disease Relevance 0.47 Pain Relevance 0.22

-inhibitor (0,1 mM) followed IL-1?

Positive_regulation (followed) of IL-1

15) Confidence 0.49 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2952629 Disease Relevance 0.16 Pain Relevance 0

It is also conceivable that the unavoidable injury caused by cannula implantation (even after the several days of convalescence) may have promoted the activation of local inflammatory factors, thereby influencing the impact of subsequently administered IL-1?

Positive_regulation (subsequently) of IL-1 associated with convalescence, inflammation and injury

16) Confidence 0.49 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2695223 Disease Relevance 0.90 Pain Relevance 0.29

levels.30 In agreement with this finding, the reduction of hippocampal neurogenesis normally associated with chronic stressor exposure was prevented in IL-1 type 1 receptor knockout mice.31 Likewise, alterations of hippocampal neurogenesis were reported in adult transgenic mice over-expressing IL-6,31 and administration of the bacterial endotoxin lipopolysaccharide (LPS) suppressed neurogenesis while concomitantly elevating IL-1?

Positive_regulation (elevating) of IL-1 associated with targeted disruption and neurodegenerative disease

17) Confidence 0.49 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2695223 Disease Relevance 1.37 Pain Relevance 0.52

As a first step to determining the utility of the IL-1 CIA model as a drug screen, we examined the ability of various known anti-inflammatory and anti-arthritic drugs to modify the IL-1 mediated enhancement of CIA in both rats and mice.

Positive_regulation (enhancement) of IL-1 associated with inflammation and arthritis

18) Confidence 0.48 Published 1991 Journal Agents Actions Section Abstract Doc Link 1950817 Disease Relevance 0.95 Pain Relevance 0.51

This intervention did not affect IL-1beta gene transcription but prevented the increase in IL-1beta plasma levels.

Positive_regulation (increase) of IL-1 in plasma

19) Confidence 0.45 Published 2010 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 20637792 Disease Relevance 1.39 Pain Relevance 0.95

Reverse transcription-polymerase chain reaction analysis of total RNA from whole lung was performed to assess the induction of TNF-alpha and IL-1 mRNAs as markers of NF-kappaB activation.

Positive_regulation (activation) of IL-1 in lung

20) Confidence 0.45 Published 2000 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 10734156 Disease Relevance 0.26 Pain Relevance 0.19

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