Poppers and Immunosuppression

[Smoothstone]

Research to determine if and how poppers are immunosuppressive continues. To date there has been one human study with the remainder studying the effects of poppers on mice and rats. 

The human study ( Dax,1991 PubMed ID: 1685501) found that natural killer cell function was immediately suppressed 30% and took 4 days to recover to baseline. The number of participants,gay male volunteers who resided at the Addiction Research Center,  was small and the dose of poppers was moderate....but the initial 3 inhalations resulted in an immediate suppression of natural killer cell function.

Gay constituents from Hollywood and West Los Angeles persuaded Congressional reps to mandate a NIDA human study. Congress directed NIDA to report back in 6 months. Allegations about homophobic intent are misdirected. Rep. Mel Levine, Los Angeles, and Rep. Henry Waxman,chair of the health services committee were responding to their concerned gay constituents.

Subsequent Rat and mice studies have found inhalation of poppers to result in:
reduced the induction of specific cytotoxic t-cells,
reduced macrophage tumoricidal activity,
increased tumor incidence,
increased tumor growth rate,
affected accessory cells, altering t-cell functions indirectly,
impaired signaling through macrophage NF-kappaB pathway
NF-kappaB-dependent induction of macrophage nitric oxide synthase and subsequent production of nitric oxide were consequently inhibited,
IL-1Beta was inhibited at both transcriptional and post-translational levels.

There are issues of dosing amounts, both in frequency and quantity, as well as the significance of the facets of immune response that were affected.

You can check out the abstracts at www.pubmed.gov   and searcj these Pubmed ID numbers:
PMID  15294346   
PMID  15222982
PMID  14521929
PMID  11310851
PMID  10964667
PMID  16288974

The National Toxicology Program has determined that poppers are carcinogenic based on mice and rat inhalation studies.   See PubMed:  PMID  12594527

Do these findings mean that using poppers is significantly immunosuppressive?  Unknown. research continuing, but also accumulating.  Quantity of use, frequency of use are likely variables effecting amount of immunosuppression.  A small number of inhalations could be less immunosuppressive than heavy use. Infrequent use would likely be less immunosuppressive than regular use.

Immune suppression can increase susceptibility to infections....HIV, KS virus, etc. This concern is not prefaced on HIV/AIDS denialism. To the contrary, it assumes that HIV is a threat and recognizes that all exposures to HIV do not result in infection. Lucky for the community. 

Most people with the KS virus will not develop Kaposi's sarcoma...however, those with deteriorating immune systems because of HIV infection, or those taking immunosuppressive drugs to prevent organ transplant rejection, are more likely to develop KS.  Interestingly, transplant recipients sometimes develop Kaposi's sarcoma but the KS lesions disappear when the immunosuppressive drugs to prevent new organ rejection are stopped.

UCSF Researchers found that the amount of the KS virus among gay men has stayed constant since the beginning of the AIDS epidemic to current. However, the amount of Kaposi's Sarcoma peaked about 1992 and decreased since despite the amount of virus staying constant.  Major decreases of Kaposi's sarcoma continued after 1996 with availability of HAART....which prevented immune system deterioration.

Recent epidemiology research has found that popper use has been found to be associated with KS virus positivity. Its possible that many folks are exposed to KS but do not get infected becaused their immune system knocks it out. If KS virus is in saliva, as the epi research shows, then the KS virus might be more widespread....except some exposed folks do not get infected.

A concern about poppers is that a suppressed immune system increases susceptibility to infections....if exposed. 

I share this information as a former participant in a UCSF KS study which found that popper use was an independent risk factor for being positive for the KS virus.

[Miss Philicia]

Do these findings mean that using poppers is significantly immunosuppressive?  Unknown.

My 1425 t-cells would beg to differ.

Also, is it REALLY necessary to have two threads on poppers in one week by the same author?  I mean, the other one ended up so swell!

[milker]

here we go again...

So I DID spend the time to read those extracts (I do not have a subscription to read the entire article). I notice that there is no baseline for the ppm. Those studies use high ppms, from 300 to 1500ppm, on mice (compare the size of a mouse with a human), for 2 to 14 hours nonstop, for 14 days!!!! A human that would inhale poppers for 14 hours would die (and there are reports of people that died that way).

Already back in 1985, some scientists were asking about the relevance of the dosages:

The relevance of these dosages to human usage of these compounds is uncertain because persons who abuse aliphatic nitrites recreationally would have intermittent exposures of variable frequency at very high dosages with chemicals of unknown purity”
Lewis DM et al. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice, II. Immunotoxicity studies. J Toxicol Env Health. 1985;15:835-46.

I'm sorry for those mice and rats.

Understand that when the first "batch" of gay patients with KS were diagnosed, back in 1982, most were using poppers, and nobody could imagine that there would be a virus that would only attack gay people, that didn't make any sense. So the initial studies started looking at substance abuses like poppers, but it was finally discovered that this disease was actually due to a virus, then by learning how the virus was being transmitted, it became clearer as why gay people were more likely to get infected.

Now that most of the scientists understood that it was a virus, some people continued to blame KS on poppers, and that unfortunately led to denialism, where people said that they could bareback as long as they didn't inhale poppers, they wouldn't get KS (which was the only "visible" OI, the only thing that could scare people and force them to protect themselves)

There has not been a real study that proves any connection between poppers and KS in humans. The only studies have been done on mice, at ppm levels that are not comparable to the average poppers user.

Like every chemical substance inhalation, the body WILL have a immunoreaction, this reaction will be different whether you inhale cigarette smoke or oven cleaner fumes. All substance abuse IS dangerous for the body, there is no question about that; so by extrapolation you could say that someone who abuses poppers AND is HIV+ is compromising its immunoresponse, and is more likely to get opportunistic infections. No need to be a rocket scientist to understand that. But saying that poppers=KS is incorrect.

Milker.

[Smoothstone]

The results of the human study seem most relevant.  The safety monitoring committee would approve only 3 inhalations at a time because of concerns about safety. There were recommendations to have study participants take a range of inhalations but these were not allowed.  In any event the immunosuppression in humans was immediate.

We have agreement that dose is important, both quantity of inhalations, and frequency of use.

It would be helpful if NIDA would sponsor another human study to look at the immune system effects of popper use...both on HIV negative and HIV positive ...both on KS virus positive and KS virus negative...

No one is claiming that poppers=KS, though historically that was one possibility considered that was discounted with the discovery of the KS virus.  The hypothesis is that poppers may be immunosuppressive  increasing susceptibility to infections....KS virus, bacteria, HIV, etc...

Prevalence of popper use and the cited findings, limitations acknowledged, warrant more research.

The KS puzzle has not been solved. There are clues which can be explored. 

[milker]

So can we agree to agree that there is no conclusive data, and that it would be nice to sometime has a real study be done, and hope that the scientists will spend more time trying to find a cure and come back to KS and poppers studies when they have spare time?

Milker.

[Miss Philicia]

No one is claiming that poppers=KS, 

Yet you just seemed to in another thread a week ago.  Odd how that works, isn't it?

[cokaine]

Thanks for the article Smooth!

Let's be realistic, poppers are not good for you. For those trying to pretend it has no effect in your body, bravo.

[Miss Philicia]

Something tells me alcohol is probably worse for you, as well as smoking.  I think most of us are simply seeking some rational context here, but I don't have high hopes of that actually occurring in this jihad environment.

[Cerrid]

It would be helpful if NIDA would sponsor another human study to look at the immune system effects of popper use...both on HIV negative and HIV positive ...both on KS virus positive and KS virus negative...

It has been extensively proven that the herpes virus HHV-8 in combination with an impaired immune system is the causative agent of KS. Besides, since the introduction of HAART, the incidence of KS has fallen dramatically. So, apart from pure academic interest, what's the point in carrying out yet another study on this tiring topic which has absolutely no relevance to the treatment of KS? Wouldn't you agree that research money and work force could be spent more wisely on some more important issues concerning HIV?