COX-2 inhibitors impact on the effiency of inflammatory repsonse?

[fredrik]

There is one thing that I have been thinking about, but never found a satisfactory answer too:

 

When people take common NSAID drugs, it obvioulsy typically reduces symptoms and makes the patient feel less discomfort, but to what extent does this manipulation of symptom reduction, compromise the bodys effiency at fighting the problem?

 

I am aware of the fact that sometimes the body may overreact and thus this sypmtom reducing drugs can be used and the body still have no problem fighting the problem.

 

But what are the exceptions to this rule? Are there any research on what impact the typical NSAID drugs have on the immune system? I'm not talking about the COX-1 related side effects but I'm more curious if someone reducing the inflammatory response at some point may worsen things? Like disarming the body, while fighting a battle?

 

For example cancers? Would COX-2 inhibitors have any impact whatsoever on the bodys intrinsic healing power in such a case?

 

What about either diseases?

 

Can someone give a direct response, or know of links to papers on this?

 

/Fredrik

[Revenged]

COX inhibition causes reduced thromboxane-A2 and reduce prostaglandins production both of which are involved in healing after inflammation... If you look into the effects of the products reduced by COX inhibitors then you should find out more information...

 

NB. COX inhibitiors don't cause cancer...

[JamesDiotte]

I am pretty sure that there are COX-Inhibitors that are actually used for treating cancer. I remember reading, not to long ago, that a few scientists substituted a couple silicon atoms for carbon atoms in Indometacin and the new chemical was suprisingly less toxic and more effective at killing cancer cells (ecspecially pancreatic). It also said that Indometacin itself is used for cancer because, for reasons not yet clearly understood, it kills cancer cells. I read further into the use of NSAID for cancer and found that they cause greater expression of tumor supressor genes (Im not exactly sure myabe someone else can ellaborate more on the subject).

[fredrik]

Thanks for your comments!

 

My original question was more general in nature, but cancer was just an interesting example. Yes I've also read that the inflammation and some gene involved in it are linked to tumour development in already existing cancers and that COX inhibitors in this special case seem to repress tumour growth. This is definitely interesting. I haven't looke up the details though.

 

But I wonder if this is to be considered a special case or not. What about other systemic threats, like more dangerous bacterial and virus infections, where the competition is tighter and the body really needs to focus it's full power to deplete the anomaly?

 

If there are nothing but good sides of COX inhibitors from the point of view of healing the body, what are the past conditions that caused the body to develop such defense? I've seen same scattered cases of special conditions in children (don't remember exactly hough) where NSAID drugs are disadvised because using them may severly worsen the condition. I don't remember now but it wasn't cancer, it was some viral or bacterial infection.

 

So perhaps the cases where these drugs are bad are rare enough to be considered exceptions?

 

What about the possible feedback from the brain? A drug that reliefs pain and makes you "feel better", could that also influence the immune system in some kind of "placebo like" effect? Placebo isn't meant to imply it isn't real thogh, it's just to reflect that from I've seen severe depressions may drop your immune system power too? Suggesting that also the opposite, that the brain can perhaps sharpen the immune system? Anyone think that can be a factor?

 

/Fredrik

[Revenged]

I read further into the use of NSAID for cancer and found that they cause greater expression of tumor supressor genes (Im not exactly sure myabe someone else can ellaborate more on the subject).

 

I've never heard of NSAIDs for cancer but yes they do exist... but remember that cancers are caused by mutations of tumour suppressor genes and oncogenes - so i'm not entirely sure if greater expression of tumour supressor genes is necessarily helpful...

 

The standard chemotherapy is a combination treatment e.g. bleomycin, cisplatin, etoposide, methotrexate and fluorouracil... Each treatment works by inhibition of DNA replication in some way... Bleomycin breaks phosphate bonds in the DNA backbone generating free radicals, cisplatin forms bonds between the two double strands of DNA preventing replication, etoposide is a DNA topoisomerase inhibitor, methotrexate and fluorouracil are inhibitors of folate metabolism... But the clear problem with these drugs is that they target ALL proliferating cells and so they are very toxic...

[Revenged]

So perhaps the cases where these drugs are bad are rare enough to be considered exceptions?

 

Vioxx (selective COX-2 inhibitor) was banned from use because of it's adverse reactions... I've added a link because I don't know that much about it...

 

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

 

The COX inhibitors that are more commonly used are more selective for COX-1 (so doesn't have the same adverse reactions as Vioxx)... The main problem with aspirin and ibuprofen is gastric ulceration, which is caused by COX inhibiting production of prostaglandin E2, which leads to increased gastric acid production... Paracetamol (centrally acting COX inhibitor but not a NSAID) is dangerous because it is metabolised to the liver to form a free radical... Normally glutathione in the liver removes the free radical but supplies of glutathione are limited and in overdose this free radical can cause potentially lethal liver and kidney failure...

[JamesDiotte]

I've never heard of NSAIDs for cancer but yes they do exist... but remember that cancers are caused by mutations of tumour suppressor genes and oncogenes - so i'm not entirely sure if greater expression of tumour supressor genes is necessarily helpful...

 

Yeah Im not exactly sure, it might be inhibition of expression of the tumor supresor genes, I just remember it having something to do with Tumor supressors.

[konstantin]

about involvement of COX-2 in cancer development.

that is link may-be will be useful for you http://www.nature.com/jid/journal/v126/n1/abs/5700014a.html;jsessionid=23B93A64EAC5B80D6194A7E0099EC13E

and you can easily find a lot of articles related to cancer, COX-2 and prostaglandins in pubmed.

as to infection, bacteria entered into our body and provoke inflammation, if we will not control this inflammatory process it can lead to overexpression of inflammatory mediators such as prostaglandins, and in conclusion can get septick shock "death".

therefore, scientists focus on the inhibition of such key point enzymes as COX-2, and of course other mediators of inflammation as iNOS or cytokines TNF-a, IL-1b and so on.

Inflammation is necessary process in host defense but overexpression can damage host body itself....

[Revenged]

excessive inflammatory responce can be dangerous in allergy as well e.g. anaphylaxic shock and asthma attack... and of course in allergy, e.g. in hayfever, the inflammatory process has no useful function...

[konstantin]

Why?!!! it has no any usefulness, it kills bacteria which disrupts balance in our body. in addition cytokines attract lymphocytes and they memorize specific antigen.....at this point we have link between innate and adaptive immunity.

[Revenged]

i'm was talking specifically about allergy...

 

e.g. there is no useful function in having an acute inflammatory responce against harmless things such as pollen in hayfever...

[konstantin]

mmmmmm yeah sorry, I misunderstood you.

you are absolutely right...

[JackMuChabas]

Not a good drug period, no uses in the biology strata of blood or the macro estemic polor functions. Part of a poison derevitive not designed to do anything but relieve the immunological response through the nervous system. Basically mask pain.