More evidence inflammation not linked to CPPS - Question

[rider fan]

I have a question about the latest research study that was posted. I'm a bit surprised because I always thought that the nerves and muscles in the pelvis were capable of causing inflammation, as stated in the pelvic myoneuropathy page. I thought this is why some men with non-bac cp can get physical changes in their prostate.

Am I confused?

[webslave]

It's complex. If you take a biopsy of the prostate of men with chronic prostatitis / chronic pelvic pain syndrome you are not likely to find inflammation (histological inflammation). Yet uros frequently see WBCs in EPS, so where are they coming from? And other studies looking at more subtle markers of inflammation, like interleukin and other cytokines, do often find signs of inflammation in prostate fluids. In addition, cystoscopies often see reddened prostatic urethras and ducts.

A recent Japanese study of prostates removed because of cancer found that although leukocytosis (pus cells or WBCs) were observed both in prostate fluid and in prostate tissue, there was no correlation between the leukocyte count in prostate fluid and the intensity of (histological) inflammation. BUT, if the prostate fluids contained a lot of macrophages, a special type of bug-eating leukocyte, then there was a correlation with inflammation in the prostate tissue. What does this tell you?

Now, IL-8 is raised in men with CP/CPPS (PMID 16905241). IL-8 is made by epithelial (lining of ducts) and stromal (internal) prostate cells, so where is it coming from? The lining of the ducts, or the inside of the prostate (stroma)?



In one of the first studies to systematically characterize inflammation of the prostate in patients who had satisfied strictly defined clinical laboratory criteria for chronic prostatitis/CPPS, True et al. found that the degree of inflammation was minimal to absent in > 95% of cases in which prostate biopsies were examined. Sound familiar? They evaluated prostatic inflammation in all areas of the gland. They also found no correlation between leukocytes in the expressed prostatic secretion (prostate fluids) and in the prostate itself (tissue) in this population.

There are a whole lot of other studies, and a good overview you can read here
http://www.blackwell-synergy.com/doi/fu ... 01.02193.x

[rider fan]

So, even though no inflammation is evident in prostates of men with CPPS, markers for inflammation are infact found when examined for things like leukocytes?

Sorry, you'll have to bear with me and my simple mind.

[webslave]

Yes, in a proportion of cases, but the lack of true inflammation inside the tissue of the prostate, which would occur if the prostate were infected (as you can deduce), means that (a) there is no infection, and (2) it suggests that the inflammation is probably coming from the outer layers of the epithelium, and is caused by the nerve endings influencing mast cells in the epithelium.

[carld]

In my case, I had a high count of WBC in my EPS and macrophages as well, acording to my first Uro. That was the source of my discomfort. What caused that That's the issue. I suspected diet, stress and injury from sitting to long or vigorous sex and ejaculations, then over time my muscles in my pelvis became to tight. From those possible causes, you get pelvic myoneuropathyand neurogenic inflammation. Right Mark

[webslave]

That's right. The macrophages, if they were present in high numbers, would suggest an infection or stromal inflammation as well. The key thing is "high numbers", because the presence of some is not significant.

[rider fan]

Yes, in a proportion of cases, but the lack of true inflammation inside the tissue of the prostate, which would occur if the prostate were infected (as you can deduce), means that (a) there is no infection, and (2) it suggests that the inflammation is probably coming from the outer layers of the epithelium, and is caused by the nerve endings influencing mast cells in the epithelium.

Thankyou Webslave.

[carld]

That's right. The macrophages, if they were present in high numbers, would suggest an infection or stromal inflammation as well. The key thing is "high numbers", because the presence of some is not significant.

Ya, I don't remember if the macrophages were high or not. They did a culture and it came back negative after I think 4 or 5 days, but still did cypro for 5 weeks just in case. I did not know then what I know now because I had not found this site at the time. Oh well, live and learn.

[consuli]

I want to post some ideas, what it makes so complicated to prove/ disprove the inflammation thesis.

<excursus>
To understand why it is so difficult with prostatitis (incl. CPPS), it is helpful to have a look on well formed diagnose problem. Let us take prostate cancer.

Prostate cancer is histological very well to diagnose. Usually a small sample of prostate tissue is cut into very small slices. The tissue slices are processed with a specific colour. The colour does not work for usual healthy tissue cells, but works for cancer cells.

When you want to set up a reliable marker for prostate cancer, you need compare both, the histological results and the suspicions well explaining parameter, lets say the psa parameter. To keep this simple and stupid. You are looking for threshold value of the psa parameter, which corresponds to a histological cancer positive rate of 95% for instance. Let's say the derived critical value is 25 nanogram psa. When a doctor years later will apply the developed test, then a psa values of more than 25 nanogram psa will provide the forecast "cancer positive".
<end of excursus>

Back to prostatitis. The big big problem is, that patients have a lot of symptoms, but till now you cannot find anything in the histological observation of prostates. Another big problem is to find prostate material of >>prostatitis patients<< at all; blanking biopsy is a pain and harmful procedure. So, if you have a suspicious parameter like Interleukin-8, you cannot backtest it with the histological result.

As a histological backtest is not available researcher take the symptom score as backtest. This is also a problem, because the etiology of prostatitis is unclear and it cannot be well isolated from other diseases (chicken and egg problem).
In fact prostatitis could be a big pool of different diseases with at random same symptoms. So backtest with symptom score is problematic. Maybe some patients really have inflammation and others do not have. The "subgroup no-inflammation" is not suitable to backtest the inflammation hypothesis for the "inflammation subgroup".

Being aware of those problems it is imho the best to use lymphocyte transformation test (LTT) screening to answer the question of inflammation. The test works the following way. T-lymphoytes are collected from patients blood. Suspicious material which might be a target of t-lymphocyte defence is presented to those collected t-lymphocytes. When the t-lymphocytes are programmed to eliminate the material, they will grow, otherwise not. The test is already very successful used for the complicated borreliose diagnosis. The LTT is not limited to bacteria. By presenting certain human cells and tissue, it can also detect auto-inflammatory problems. From my point of view the cell classes in the prostate are not this high in number, that it would not be possible to construct a screening test like mentioned.

The big plus of the LTT test is it explains itself. There is no further backtesting needed.

Bye
Consuli

[calguy]

I'm with riderfan this discussion just confused the hell out of me. I thought Prostatitis was linked to chronic prostatitis / chronic pelvic pain syndrome or even caused by it. I assumed that is why all the TP and Pelvic work helped relieved symptoms of prostatitis. I did have some WBC in prostate fluid and cysto showed red inflammation. Webslave sounds like you were saying we can have no inflammation, (have patience with me too I am trying to get this). So why do all the natural supplements for inflammation help me and antibiotics help because of anti-inflammatory effects?

[webslave]

There usually is inflammation if you look at subtle markers of inflammation. Recently, researchers found that men with categories IIIa and IIIb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their expressed prostatic secretions when compared with controls (study). Visually (cystoscopy), the prostatic urethra is often inflamed. But the actual tissue inside the prostate is not inflamed (as it would be if it were infected, for instance). So there is inflammation in CPPS, at the nerve endings in the urethra inside the prostate, and often elsewhere too (bladder neck, bladder, other parts of urethra, and even testicles.

It's more useful to think of this as a nerve dysfunction than an organ dysfunction.

[consuli]

There usually is inflammation if you look at subtle markers of inflammation. Recently, researchers found that men with categories IIIa and IIIb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their expressed prostatic secretions when compared with controls (study). .

Yes, these studies are very strong hints prostatitis (incl. CPPS) is inflammatory, at least for a broader proportion of prostatitis patients. Nevertheless it is problematic to develop a standardized lab test without sharp desease definition.

Visually (cystoscopy), the prostatic urethra is often inflamed. But the actual tissue inside the prostate is not inflamed (as it would be if it were infected, for instance). So there is inflammation in CPPS, at the nerve endings in the urethra inside the prostate, and often elsewhere too (bladder neck, bladder, other parts of urethra, and even testicles.

It's more useful to think of this as a nerve dysfunction than an organ dysfunction.

From my point of view any inflammation is usually promoted by the autonomic nervous system. As long we do not know, what the immune system fights in the prostate, we cannot consider if it is an absurd reaction (dysfuntion). Only a LTT test can answer this question.

[webslave]

As long we do not know, what the immune system fights in the prostate, we cannot consider if it is an absurd reaction (dysfuntion). Only a LTT test can answer this question.

Well, we know that the immune system is not fighting anything inside the prostate, because over 95% of patients have no or minimal prostatic (stromal) inflammation. So we need to find out what is causing the epithelial inflammation. A LTT is not required in my opinion, because we have seen extensive PCR testing already.

(The lymphocyte transformation test (LTT) is an in vitro (laboratory) test which is based on the fact that lymphocytes, which have been sensitized by a certain antigen, transform into blasts and proliferate when they are again exposed to this antigen.)

[consuli]

Well, we know that the immune system is not fighting anything inside the prostate, because over 95% of patients have no or minimal prostatic (stromal) inflammation.

Maybe the inflammation is only at the surface, the epithelium.

So we need to find out what is causing the epithelial inflammation. A LTT is not required in my opinion, because we have seen extensive PCR testing already.

A PCR cannot test nanobacteria and viruses (and other unknown bugs). So the conclusion PCR negative = autoinflammatory may not always be correct.

[webslave]

A PCR cannot test nanobacteria and viruses (and other unknown bugs). So the conclusion PCR negative = autoinflammatory may not always be correct.

Viral DNA can be detected by PCR. Nanobacteria, if they indeed exist (controversial), exist, in theory, within prostatic stones, so that doesn't wash either.

In other words, a LTT would not be helpful.