INT94464

Context Info Confidence 0.41 First Reported 2000 Last Reported 2011 Negated 0 Speculated 2 Reported most in Body Documents 44 Total Number 46 Disease Relevance 31.50 Pain Relevance 12.39

cell differentiation (Hand1) nucleoplasm (Hand1) enzyme binding (Hand1) DNA binding (Hand1) cytoplasm (Hand1) nucleolus (Hand1)

Anatomy Link Frequency T-cell 5 brain 2 Th17 cells 2 Th1 cells 1 sciatic nerve 1 Hand1 (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 866 100.00 Inflammation 859 100.00 cINOD 43 99.90 methotrexate 36 99.62 Catecholamine 6 99.54 withdrawal 15 99.52 dexamethasone 11 99.52 Morphine 23 99.36 rheumatoid arthritis 256 99.20 Endogenous opioid 2 99.20

Disease Link Frequency Relevance Heat INFLAMMATION 978 100.00 Colitis 120 100.00 Repression 22 100.00 Birth Weight 2 99.96 Hypersensitivity 199 99.92 Infection 300 99.90 Reprotox - General 3 6 99.74 Autoimmune Disease 194 99.56 Targeted Disruption 126 99.40 Stroke 18 99.40

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma (Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner.

Negative_regulation (decreases) of Th1 associated with morphine

1) Confidence 0.41 Published 2004 Journal J. Neuroimmunol. Section Abstract Doc Link 14741432 Disease Relevance 0.10 Pain Relevance 0.53

These results suggest that anti-arthritic drugs including IND, DEX, MTX and AUR appear to suppress Th1 and, to a lesser extent, Th2 immune responses, and their anti-inflammatory effects on human rheumatoid arthritis might be at least in part explained by downregulation by these drugs of Th1 responses involved in the disease.

Negative_regulation (suppress) of Th1 associated with inflammation, rheumatoid arthritis, disease, methotrexate, dexamethasone and arthritis

2) Confidence 0.38 Published 2005 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 15698518 Disease Relevance 0.66 Pain Relevance 0.56

The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could activate Th2 and suppress Th1 cytokines.

Negative_regulation (suppress) of Th1 associated with endogenous opioid, narcan and cytokine

3) Confidence 0.34 Published 2000 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 11268404 Disease Relevance 0.09 Pain Relevance 0.82

These results suggest that nonsteroidal anti-inflammatory drugs may downregulate Th1 and, to a lesser extent, Th2 immune responses.

Spec (may) Negative_regulation (downregulate) of Th1 associated with inflammation and cinod

4) Confidence 0.34 Published 2003 Journal J Pharm Sci Section Abstract Doc Link 12884258 Disease Relevance 0.42 Pain Relevance 0.37

Thus, a shift in immune responses with a downregulation of Th1 and an upregulation of Th2 is thought to be necessary for fetal survival [10,103-105].

Negative_regulation (downregulation) of Th1

5) Confidence 0.33 Published 2011 Journal Biol Sex Differ Section Body Doc Link PMC3022636 Disease Relevance 0.72 Pain Relevance 0.15

IL-18 deficiency inhibits both Th1 and Th2 cytokine production but not the clinical symptoms in experimental autoimmune neuritis.

Negative_regulation (inhibits) of Th1 associated with experimental autoimmune neuritis, neuritis and cytokine

6) Confidence 0.31 Published 2007 Journal J. Neuroimmunol. Section Title Doc Link 17218016 Disease Relevance 0.37 Pain Relevance 0.48

Our interpretation on the controversy is that the previous studies on the function of CIITA in peripheral CD4+ T cells from CIITA-deficient and -transgenic mice have focused largely on repression of Th1 immunity in vivo, while Th2 bias was checked via in vitro studies.

Negative_regulation (repression) of Th1 in T cells associated with targeted disruption and repression

7) Confidence 0.31 Published 2006 Journal Journal of Korean Medical Science Section Body Doc Link PMC2721999 Disease Relevance 0.77 Pain Relevance 0

Fewer IFN-gamma and TNF-alpha producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12-/- mice, consistent with impaired Th1 functions and response.

Negative_regulation (impaired) of Th1 in sciatic nerve associated with sciatic nerve

8) Confidence 0.30 Published 2002 Journal Brain Pathol. Section Abstract Doc Link 12408228 Disease Relevance 0.85 Pain Relevance 0.64

These results suggest that anti-arthritic drugs including IND, DEX, MTX and AUR appear to suppress Th1 and, to a lesser extent, Th2 immune responses, and their anti-inflammatory effects on human rheumatoid arthritis might be at least in part explained by downregulation by these drugs of Th1 responses involved in the disease.

Negative_regulation (downregulation) of Th1 associated with inflammation, rheumatoid arthritis, disease, methotrexate, dexamethasone and arthritis

9) Confidence 0.27 Published 2005 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 15698518 Disease Relevance 0.60 Pain Relevance 0.42

It was later shown that genetic deficiency in CD40L [55] or antibody-mediated blockade of CD40L [56] resulted in attenuation of Th1 differentiation and effector function, including marked inhibition of the Th1 cytokine IFN-?

Negative_regulation (inhibition) of Th1 associated with cytokine

10) Confidence 0.26 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1298325 Disease Relevance 0.78 Pain Relevance 0.11

It has been recently shown, the effect of retinoic acid in T cells, with a decrease of the T-helper 1 (Th1) immune response and an increase of Th2 immune response in vitro [10] and in vivo [13].

Negative_regulation (decrease) of Th1 in T cells

11) Confidence 0.26 Published 2009 Journal Nutr Metab (Lond) Section Body Doc Link PMC2773769 Disease Relevance 0.93 Pain Relevance 0.22

Following withdrawal, it was found that the Th1-polarizing cytokine IL-12 was significantly decreased, providing further support for the observation that withdrawal results in Th2 differentiation by possibly impacting the generation of an appropriate innate immune response which directs subsequent adaptive Th1/Th2 responses.

Negative_regulation (decreased) of Th1 associated with withdrawal and cytokine

12) Confidence 0.26 Published 2005 Journal J. Immunol. Section Abstract Doc Link 16081842 Disease Relevance 0 Pain Relevance 1.33

We found a clear reduction in Th1 response (IL-2 and IFN-?)

Spec (clear) Negative_regulation (reduction) of Th1

13) Confidence 0.25 Published 2005 Journal Respir Res Section Body Doc Link PMC555575 Disease Relevance 0.79 Pain Relevance 0.25

, while Th1 response is defective.

Negative_regulation (defective) of Th1

14) Confidence 0.25 Published 2005 Journal Respir Res Section Body Doc Link PMC555575 Disease Relevance 1.16 Pain Relevance 0.24

-/- mice are capable of inducing significantly higher OVA-specific T cell proliferation of Th2 character [19] which might also partly contribute to suppression of a more profound Th1 response.

Negative_regulation (suppression) of Th1 in T cell

15) Confidence 0.25 Published 2005 Journal Respir Res Section Body Doc Link PMC555575 Disease Relevance 0.07 Pain Relevance 0.03

Thus, pBTLA treatment appeared to decrease the Th1 type of immune response of mice.

Negative_regulation (decrease) of Th1

16) Confidence 0.21 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2965573 Disease Relevance 0.73 Pain Relevance 0.05

The adverse outcomes include decreased birth weight, decreased cord blood cytokines levels (both TH1 and TH2), increased collagen deposition in airway and alveolar walls, abnormal lung function at birth, and suppressed ventilatory responses to postnatal hypoxia (Sekhon et al. 2002; Ueda et al. 1999).

Negative_regulation (decreased) of TH1 in lung associated with birth weight, hypoxia and cytokine

17) Confidence 0.21 Published 2006 Journal Environ Health Perspect Section Body Doc Link PMC1440793 Disease Relevance 1.06 Pain Relevance 0.23

Aberrant Stat3 activation in tumour cells promotes the secretion of immunomodulatory factors, which selectively reduce the Th1 dominated anti-tumour response [126].

Negative_regulation (reduce) of Th1 associated with cancer

18) Confidence 0.21 Published 2010 Journal Cell Div Section Body Doc Link PMC2887830 Disease Relevance 1.33 Pain Relevance 0.03

It is plausible that a host with a modestly compromised innate immune system would on one hand – avoid infertility by mounting reduced Th1 responses and on the other – be unable to optimally clear a chlamydial infection.

Negative_regulation (reduced) of Th1 in immune system associated with reprotox - general 3 and chlamydia infection

19) Confidence 0.18 Published 2008 Journal BMC Microbiol Section Body Doc Link PMC2543025 Disease Relevance 1.14 Pain Relevance 0.03

Because Th1 cells are highly sensitive to apoptosis [76], modification of their oxidative status by PPARs may help to normalize the Th1/Th2 balance.

Negative_regulation (normalize) of Th1 in Th1 cells associated with apoptosis

20) Confidence 0.16 Published 2010 Journal PPAR Research Section Body Doc Link PMC2796461 Disease Relevance 0.84 Pain Relevance 0.30

General Comments

This test has worked.