48 replies to this topic

[Lufega]

TNF-alpha plays a pivotal role in the systemic effects of having COPD/emphysema. From my research, it is obvious that keeping levels in check is the best treat all strategy. I want some ideas as to what is the best way to maintain constant low levels. Curcumin and green tea are potential candidates already. What else is out there ?

[Rational Madman]

TNF-alpha plays a pivotal role in the systemic effects of having COPD/emphysema. From my research, it is obvious that keeping levels in check is the best treat all strategy. I want some ideas as to what is the best way to maintain constant low levels. Curcumin and green tea are potential candidates already. What else is out there ?

Well, Bupropion reduces the expression of this cytokine through its indirect activation of beta adrenergic receptors, and Amitryptaline has been found to have the same effect through a similar interaction with alpha adrenergic receptors. So I think the implication is that tumor necrosis factor is adrenergically mediated through receptor activation, or the inhibition of the reuptake or transport of norepinephrine.

Edited by Rol82, 28 April 2011 - 06:09 AM.

[niner]

There's always anti-tnf Mabs. Or should I say Mab$?

[youandme]

Xanthine Derivatives


http://en.wikipedia.org/wiki/Xanthine


more


http://en.wikipedia....i/TNF_inhibitor



Sorry to quote wiki !..but sometimes there is some good stuff

[youandme]

Reduced levels of TNF(alpha) in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks


http://www.mendeley....atin-8-weeks-7/

[youandme]

Zinc ..perhaps ?!



http://www.ncbi.nlm....pubmed/21514808

[youandme]

There's always anti-tnf Mabs. Or should I say Mab$?

Wondering do we know by how much Anti-mabs reduce TNF in the body given usual treatment regime ? % ?

[youandme]

Here is a good one !

Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress.

http://www.ncbi.nlm....xidative stress.


"TNF-alpha production by whole blood was 34.4% lower after 26 days of drink consumption.."


Can I believe this...hmmm !

[youandme]

One more for the Tomatoe and the Rat !...



Lycopene from tomatoes partially alleviates the bleomycin-induced experimental pulmonary fibrosis in rats.

http://www.ncbi.nlm....pubmed/19083398

"These findings suggest that the suppression of oxidative stress, the reduction of plasma TNF-alpha and NO levels, and the down-regulation of TNF-alpha in lungs contribute to the alleviation of PF in rats administered lycopene."

Edited by youandme, 28 April 2011 - 01:52 PM.

[youandme]

The Counter Study...TNF Increases with Tomato consumption lol



Prolonged Tomato Juice Consumption Has No Effect on Cell-Mediated Immunity of Well-Nourished Elderly Men and Women



http://jn.nutrition....7/1719.full.pdf


"TNF-a and IL-4 secretion were increased at the end of the intervention period,"

Edited by youandme, 28 April 2011 - 02:17 PM.

[youandme]

N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro.


http://www.ncbi.nlm....pubmed/20560295

[Lufega]

Flax ?

Saudi Med J. 2011 Apr;32(4):369-75.
Manipulation of flaxseed inhibits tumor necrosis factor-alpha and interleukin-6 production in ovarian-induced osteoporosis.
Abdelkarem HM, Abd El-Kader MM, Kasem SA.
Source
Biochemical Nutrition, Food Science and Nutrition Department, Food Science & Agriculture Collage, King Saud University, PO Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. Tel. +966 (1) 530707977. Fax: +966 (1) 4775406. E-mail: halaabdelkarem@yahoo.com.

Abstract
OBJECTIVE:
To evaluate the potential effects of whole flaxseed (FS), and/or flax oil (FO) incorporation into the diet on the level of pro-inflammatory cytokines in ovariectomized (OVX) rats model of osteoporosis.
METHODS:
This study was performed in the Food Science & Agriculture Collage, King Saud University, Kingdom of Saudi Arabia from October to December 2009. Forty-eight, 3-month-old female Sprague-Dawley rats were randomly divided into 6 groups: Group 1 - sham + control diet; Group 2 - OVX rats + basal diet; Group 3 - OVX + 20% whole FS; Group 4 - OVX rats + 40% FS; Group 5 - OVX rats + 5% FO; Group 6 - OVX rats + 10% FO. All OVX rats underwent bilateral ovariectomy. The experiment was continued for 2 months. Serum bone alkaline phosphatase (B-ALP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), calcium (Ca), phosphorous (P), and magnesium (Mg) were measured.
RESULTS:
A significant increase of serum IL-6 and TNF-alpha concentrations were observed between OVX rats when compared with Group 1, while there was no significant difference in the activity of B-ALP, serum Ca, P, and Mg among all groups. A remarkable significant decrease of serum levels of IL-6 and TNF-alpha was observed in the group of rats that were fed with FS (Groups 3 and 4) and FO (Groups 5 and 6).
CONCLUSION:
This study suggests that FS and FO might be useful in the prevention of estrogen-deficiency induced osteoporosis via decreasing osteoclastogenesis. Further studies are needed to demonstrate their efficacy in humans by using bioactive components of FS, and to clarify their mechanism of action.

PMID:21483995 [PubMed - in process]

From another study, the optimal dose seems to be 14 g which roughly equals 1 tablespoon a day. PMID:19568181

Edited by Lufega, 28 April 2011 - 02:49 PM.

[youandme]

I think the Flax has it !?




The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids

Source
Rheumatology Unit, Royal Adelaide Hospital, Australia.


Abstract
The effect of a flaxseed oil-based diet on tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNF alpha and IL-1 beta production by approximately 30%. Fish-oil supplementation (9 g/d) continued for a further 4 wk; TNF alpha and IL-1 beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNF alpha or IL-1 beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n--3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha-linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to approximately 1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF alpha and IL-1 beta synthesis.



I dont think anyone is going to digest 9g/d of Fish oil supps ! especially after the Prostate scare !

[Lufega]

Carnitine also lowers TNF-a rather well.

Mediators Inflamm. 1993;2(7):S33-6.
Anaesthetics modulate tumour necrosis factor alpha: effects of L-carnitine supplementation in surgical patients. Preliminary results.
Delogu G, De Simone C, Famularo G, Fegiz A, Paoletti F, Jirillo E.
Source Anaesthesiology and Intensive Care University "La Sapienza" Rome Italy.

Abstract
Both anaesthetics and surgical trauma could strongly affect the production of tumour necrosis factor alpha (TNFalpha). During in vitro experiments the authors found that anaesthetics modulate the production of TNFalpha by peripheral blood mononuclear cells. Notably, Pentothal strongly increased the production of the cytokine as compared to both lipopolysacchride treated and control mononuclear cells, whereas in supernatants from Leptofen driven mononuclear cells TNFalpha was strongly reduced. On the other hand, Pavulon did not significantly affect the cytokine production. In the in vivo study, in an attempt to ameliorate the metabolic response to surgical trauma, L-carnitine was administered to 20 surgical patients, then the circulating TNFalpha was measured. The results indicate that the levels of circulating TNFalpha were strongly increased following surgery and that L-carnitine administration resulted in a strong reduction of TNFalpha. Thus, the data suggest that L-carnitine could be helpful in protecting surgical patients against dysmetabolism dependent on dysregulated production of TNFalpha.

PMID:18475568

Edited by Lufega, 28 April 2011 - 03:18 PM.

[david ellis]

Fucoxanthin and fish oil(extract of wakame, a sea weed)inhibits TNF. Maybe you can lose weight too.


http://www.ncbi.nlm....pubmed/17715888

[Lufega]

Magnesium. If I could hit the inflammation in the lung directly, I can prevent the inflammatory cytokines from spilling over onto the rest of my body. For this, I've been toying with using inhaled magnesium on a regular basis. I've tried it a couple of times with epsom salt and I felt better, although a bit lightheaded.

TNFalpha receptor knockout in mice reduces adverse effects of magnesium deficiency on bone.
Rude RK, Wei L, Norton HJ, Lu SS, Dempster DW, Gruber HE.
Source
Keck School of Medicine and Orthopaedic Hospital, University of Sourthern California, Los Angeles, CA, 90033, USA. rrude60075@aol.com


Abstract
Epidemiologic studies have linked low dietary magnesium (Mg) intake to osteoporosis. Dietary Mg restriction in animal models has demonstrated a decrease in bone mass and an increase in skeletal fragility. The exact mechanism for the decrease in bone mass is not clear but a decrease in osteoblast number and an increase in osteoclast number (Oc.No/B.Pm) suggests an uncoupling of bone formation and bone resorption favoring skeletal loss. Mg depletion results in an increase in inflammatory cytokines, which could explain the increase in bone resorption. We have previously demonstrated an increase in TNFalpha in bone from Mg deficient rodents. Here we report results of a 3 week study of a low magnesium (LM) diet and normal Mg diet in 35-day-old TNFalpha receptor knockout mice (TNF-r-KO) versus wild type (WT) control mice. Our results indicated that a LM diet resulted in a greater increase in Oc.No/B.Pm in the WT mice, with a trend toward greater eroded bone perimeter, as compared to TNF-r-KO. These findings suggest that TNFalpha may play a role in Mg deficiency-induced bone loss.

PMID:19919525 [PubMed - indexed for MEDLINE]

[youandme]

Its hard to know the levels of inhibition they all can achieve...also to compare with biologics efficacy...anyone know more ?

It would be something if one could achieve the same inhibition result as per anti-mabs

Remembering If one effectively lowers TNF Alpha excessively then infections become more an issue.

Edited by youandme, 29 April 2011 - 12:44 AM.

[Lufega]

Its hard to know the levels of inhibition they all can achieve...also to compare with biologics efficacy...anyone know more ?

It would be something if one could achieve the same inhibition result as per anti-mabs

Remembering If one effectively lowers TNF Alpha excessively then infections become more an issue.

Good point ! Too much inhibition and you're immune suppressed. Is there a way I can test myself without seeing the good Doc ? I would happily volunteer to test the inhibitory capacity of different compounds. In the meanwhile, I'm waiting for roflumilast to be approved !

[niner]

Magnesium. If I could hit the inflammation in the lung directly, I can prevent the inflammatory cytokines from spilling over onto the rest of my body. For this, I've been toying with using inhaled magnesium on a regular basis. I've tried it a couple of times with epsom salt and I felt better, although a bit lightheaded.

TNFalpha receptor knockout in mice reduces adverse effects of magnesium deficiency on bone.
Rude RK, Wei L, Norton HJ, Lu SS, Dempster DW, Gruber HE.

Epidemiologic studies have linked low dietary magnesium (Mg) intake to osteoporosis. Dietary Mg restriction in animal models has demonstrated a decrease in bone mass and an increase in skeletal fragility. The exact mechanism for the decrease in bone mass is not clear but a decrease in osteoblast number and an increase in osteoclast number (Oc.No/B.Pm) suggests an uncoupling of bone formation and bone resorption favoring skeletal loss. Mg depletion results in an increase in inflammatory cytokines, which could explain the increase in bone resorption. We have previously demonstrated an increase in TNFalpha in bone from Mg deficient rodents. Here we report results of a 3 week study of a low magnesium (LM) diet and normal Mg diet in 35-day-old TNFalpha receptor knockout mice (TNF-r-KO) versus wild type (WT) control mice. Our results indicated that a LM diet resulted in a greater increase in Oc.No/B.Pm in the WT mice, with a trend toward greater eroded bone perimeter, as compared to TNF-r-KO. These findings suggest that TNFalpha may play a role in Mg deficiency-induced bone loss.

I think it's a stretch to go from effects in Mg depleted animals, then apply it to a human with normal to above-average Mg levels. The effect on cytokines may level off at a very low level of Mg, such that adding more from a normal level might have no effect on cytokines. You just can't tell that from this paper.

[niner]

Its hard to know the levels of inhibition they all can achieve...also to compare with biologics efficacy...anyone know more ?

It would be something if one could achieve the same inhibition result as per anti-mabs

Remembering If one effectively lowers TNF Alpha excessively then infections become more an issue.

That's a very good question. I think we spend a lot of time considering compounds that have an interesting effect at some (usually huge, and often in vitro) dose, but it's really important to keep the magnitude of the various effects in mind. I don't know the magnitudes for the things described above, but I have a suspicion that the Mabs are highly effective. Increased infection risk is a common side effect with them, but I've never heard of infection being a problem with omega-3 fatty acids, even at high doses.

[youandme]

Yeah !

Y'know I find it bewildering that a study/s such as comparing efficacy of TNF A inhibitors such as anti-mabs with simpler molecules does not exist has not been done.....a LOT of money goes into prescriptions for anti-mabs


first just for example....

9g/day of Fish Oil inhibits TNF Alpha by 74% ....what can an anti-mab do ?

...74% is a lot...only 26% remaining....A belated easter egg for anyone that can tell the data on anti-mabs !

Edited by youandme, 29 April 2011 - 05:41 AM.

[youandme]

Anti-tumor necrosis factor (TNF) therapy in rheumatoid arthritis: correlation of TNF-alpha serum level with clinical response and benefit from changing dose or frequency of infliximab infusions.


http://www.ncbi.nlm....pubmed/16095114



"TNF-alpha serum levels pre-infliximab infusion were significantly higher in the active disease group 76.1 pg/ml than the inactive group 38.0 pg/ml (P < 0.02). Whereas TNF serum level significantly dropped post infliximab in the inactive group (P < 0.05), it did not drop in the active group. The mean level of the post-infusion TNF-alpha serum level was higher (76.6 +/- 93.4 ng/ml) in the-active than the mean level of the post-infusion serum TNF-alpha levels in the inactive group (26.4 ng/ml +/- 7.9) P < 0.01 using the t-test. Increasing the frequency was superior in RA patients' clinical outcome than increasing the dose of infliximab infusions."


Doh..anyone good at maths who could put a % figure to tell by how much Infliximab reduced/increased TNF A in both groups !?...it looks like about 30% reduction in the inactive disease group (rough guestimate.)

I think we have to remember there are so many variables here....the above study shows that when someone has active disease and higher levels of TNF then dosing/frequency is critical and changes the efficacy of Infliximab's TNF A inhibition over a healthy control.

How would 9g/d of Fish Oil fare in the same circumstances....nobody knows ?!

Edited by youandme, 29 April 2011 - 06:17 AM.

[david ellis]

Magnesium. If I could hit the inflammation in the lung directly, I can prevent the inflammatory cytokines from spilling over onto the rest of my body. For this, I've been toying with using inhaled magnesium on a regular basis. I've tried it a couple of times with epsom salt and I felt better, although a bit lightheaded.

My son-in-law had good results with inhaled glutathione fighting valley fever.

edited link to work

Edited by david ellis, 29 April 2011 - 06:58 AM.

[Lufega]

Magnesium. If I could hit the inflammation in the lung directly, I can prevent the inflammatory cytokines from spilling over onto the rest of my body. For this, I've been toying with using inhaled magnesium on a regular basis. I've tried it a couple of times with epsom salt and I felt better, although a bit lightheaded.

My son-in-law had good results with inhaled glutathione fighting valley fever.

edited link to work

David,

Can you give me more information on this ? Glutathione is heavily consumed in COPD faster than NAC can replenish it! Thanks !

[Lufega]

What would be some negative consequences of consuming 9 gr fish oil every day ? Ideally, maybe it would be best to do a loading phase of say, 1 week at 9 gr fish oil. Then reduce this amount to 9 gr once per week and the other 6 days, consume something like flax oil, which also reduces TNF-a to a lesser extent. I suppose this would avoid some negative side effects/oxidation potential from using too much fish oil. Bleh.

[youandme]

I guess the potential negatives from 9g/day would be risk of infection or and cancer...(or and perhaps inceased Autoimmune Condition risk)
Noting the other thread for the study revealing a link between aggressive form of prostate cancer and DHA from fish.


74% reduction is huge if anywhere near correct. The study mentioned EPA not DHA.
Cancer and Infections are known to be issues with anti-mab use...as are more autoimmune manifestations.

Edited by youandme, 30 April 2011 - 11:29 AM.

[youandme]

One of the issues ...measurement of TNF Alpha....Ive had a lot of tests for my issues..yet they have never checked TNF....why? is it hard to do and thus costly ? (Im going to ask next time round)...and what IS a safe level..a therapeutic level ?

Another issue is that not all TNF Alpha inhibitors work the same way...so percentage of inhibition may mean something different in the real world per Inhibitor.


As I said I find it amazing that as yet no studies have been conducted to compare anti-mabs with simple molecule TNF A inhibitors....there is a chance that Fish Oil (according to the stated study) is at least as efficient at this job as the veryvery very very expensive biologics......I assume the reason is quite simply..no one wants to go against pharma...or perhaps funding will dry up...and then who would fund such a study anyway.

Then there is the accumalitive approach of TNF Alpha inhibition...taking so many supplements and eating certain foods could increase the inhibition....and what if you are on anti-mab therapy...perhaps a good idea not to take supplments like fish oil or flax etc etc... !

Seems an area where research needs to pull together and find out more.

[Rational Madman]

While targeting this cytokine may yield therapeutic benefits for some subjects, caution should be warranted, because it also plays a role in memory and cell growth.

Edited by Rol82, 01 May 2011 - 04:30 AM.

[youandme]

Searching older forum threads threw up more information about TNF Alpha from a previous thread.....adding the link for completeness

http://www.longecity...pha-inhibitors/

[Lufega]

SAMe also decreases TNF-alpha and this mechanism accounts for its anti-inflammatory properties. It is also a PDE4 inhibitor, which is beneficial for COPD AND it raises cAMP. It also tickles me in a funny way and makes me laugh. The abstracts says it's a free article but I can't access it as of yet.

J Pharmacol Exp Ther. 2011 May;337(2):433-43. Epub 2011 Jan 25.
S-Adenosylmethionine Decreases Lipopolysaccharide-Induced Phosphodiesterase 4B2 and Attenuates Tumor Necrosis Factor Expression via cAMP/Protein Kinase A Pathway.
Gobejishvili L, Avila DV, Barker DF, Ghare S, Henderson D, Brock GN, Kirpich IA, Joshi-Barve S, Mokshagundam SP, McClain CJ, Barve S.
Source
Department of Medicine, Pharmacology and Toxicology, University of Louisville Medical Center, 505 S. Hancock St., CTR Bldg., 5th Floor, Room 515, Louisville, KY 40202. shirish.barve@louisville.edu.


Abstract
S-Adenosylmethionine (SAM) treatment has anti-inflammatory, cytoprotective effects against endotoxin-induced organ injury. An important component of the anti-inflammatory action of SAM involves down-regulation of the lipopolysaccharide (LPS)-induced transcriptional induction of tumor necrosis factor-α (TNF) expression by monocytes/macrophages. We examined the effect of SAM on expression and activity of LPS-induced up-regulation of phosphodiesterase 4 (PDE4), which regulates cellular cAMP levels and TNF expression. LPS treatment of RAW 264.7, a mouse macrophage cell line, led to the induction of Pde4b2 mRNA expression with no effect on Pde4a or Pde4d. SAM pretreatment led to a significant decrease in LPS-induced up-regulation of Pde4b2 expression in both RAW 264.7 cells and primary human CD14(+) monocytes. Of note, the decreased Pde4b2 mRNA expression correlated with the SAM-dependent increase in the transcriptionally repressive histone H3 lysine 9 trimethylation on the Pde4b2 intronic promoter region. The SAM-mediated decrease in LPS-inducible Pde4b2 up-regulation resulted in an increase in cellular cAMP levels and activation of cAMP-dependent protein kinase A (PKA), which plays an inhibitory role in LPS-induced TNF production. In addition, SAM did not affect LPS-inducible inhibitor of nuclear factor-κB degradation or nuclear factor-κB (NF-κB)-p65 translocation into the nucleus but rather inhibited NF-κB transcriptional activity. These results demonstrate for the first time that inhibition of LPS-induced PDE4B2 up-regulation and increased cAMP-dependent PKA activation are significant mechanisms contributing to the anti-TNF effect of SAM. Moreover, these data also suggest that SAM may be used as an effective PDE4B inhibitor in the treatment of chronic inflammatory disorders in which TNF expression plays a significant pathogenic role.

PMID:21266552