Share Facebook
Crohn's Disease Forum » Books, Multimedia, Research & News » Infliximab modifies response to MAP infection


07-27-2014, 05:00 PM   #1
JMC
Senior Member
 
JMC's Avatar
 
Join Date: Sep 2011
Location: London, United Kingdom
Infliximab modifies response to MAP infection

Interesting new paper: Infliximab therapy increases the frequency of circulating CD16(+) monocytes and modifies macrophage cytokine response to bacterial infection
07-27-2014, 07:18 PM   #2
Robrich
Senior Member
 
Robrich's Avatar
 
Join Date: Oct 2012
Location: SoCal

My Support Groups:
Thanks but what does that mean?
Sounds not so great if it increases TNF response, if thats what it's saying
__________________
DX. Crohns 50 yrs. with fistulas for 20 years until remicade
Meds: MTX,ENTYVIO 9/14' augmentin,
pred. 10mg.
probiotics
d3, calcium, k2' magnesium, resveratrol,
Turmeric,paleo, bone broths
Past: humira no response after 6 mos., remicade amazing for 10 years then stopped working.
Entocort
6mp, Imuran never helped nasty side effects liver problems, caught pneumonia
Asacol, rowasa no response
Flagyl worked well but got PN cipro same.
07-27-2014, 07:36 PM   #3
xeridea
Senior Member
 
xeridea's Avatar
JMC this is an interesting proposition, especially if you ascribe to theory that CD is a macrophage deficiency issue. Just going by the abstract it seems it's boosting macrophage secretion, which then goes to normalize the body's natural mechanism for bacterial clearing. I'm going to try to get full article to see if I can digest what it says.
07-28-2014, 01:09 PM   #4
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
Nothing wrong with TNF-alpha itself, it can induce fevers to kill bacteria, it increases blood flow during infections, and most importantly it helps set in motion the adapative immune response.

It's the chronic release of TNF-alpha by macrophages that's an issue. TNF-alpha will help mature the dendritic cells, those cells will go up to lymph nodes, and they will chronically stimulate the adaptive immune system. The dendritic cells act as APC, I posted a pic of an APC in the wiki section. Antigen Presenting Cell. They present antigen to the lymphocytes, and normally the immune response subsides, once lymph nodes take care of the threat, but if the bacteria isn't killed, macrophages will keep releasing TNF-alpha and it will keep stimulating the adaptive immune response, and you get a viscious circle of inflammation.

Normally we need TNF-alpha, but if it's chronically released, or if it's overstimulated (like in sepsis, tons of TNF-alpha is released during sepsis), it's really bad.

The reason those bacteria aren't properly killed is probably because those NOD2, ATG16L1 and interleukin variants don't allow a macrophage to properly complete autophagy steps and it's chronically activated.
07-28-2014, 01:28 PM   #5
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
JMC this is an interesting proposition, especially if you ascribe to theory that CD is a macrophage deficiency issue. Just going by the abstract it seems it's boosting macrophage secretion, which then goes to normalize the body's natural mechanism for bacterial clearing. I'm going to try to get full article to see if I can digest what it says.
The fact macrophages line the intestine from top to bottom in huge numbers, and the fact our gene variants directly affect the ability of macrophages to clear bacteria, leave very little doubt that CD centers around innate immunodeficiencies. If you stimulate those macrophages or stimulate autophagy in those macrophages (vit D might stimulate autophagy through NOD2), in theory they would have less issues dealing with bacteria and you wouldn't have a chronically stimulated immune system since those macrophages will stop releasing cytokine that stimulate the immune system.

If you look at crohn's disease from an immunodeficiency angle, a lot of things suddenly make sense, particularly our innate immune system, or primary immune system, whatever people choose to call it.
07-28-2014, 03:02 PM   #6
Lady Organic
Forum Monitor
 
Lady Organic's Avatar
From what I understand the Qubiologics vaccine going on trial in Vancouver is about a treatment that stimulates the macrophages so they can work properly. Is the anti-map vaccine working in similar way?
__________________
''UC-like Crohn's'' since 2001:
on: 25mg 6-MP (purinethol)+ B12 shots
minor hands/wrists chronic arthritis since 01/2013

Diet: ''IBD-AID'' : http://www.nutritionj.com/content/13/1/5+ organic food only
suppl Curcuminoid extract, Inulin,psyllium, apple pectin, Vitamin D

past meds:
pred 50mg, 5-ASA, cortifoam, Imuran (failed) Purinethol (success) methotrexate (failed CD and arthritis).
07-28-2014, 03:50 PM   #7
xeridea
Senior Member
 
xeridea's Avatar
The fact macrophages line the intestine from top to bottom in huge numbers, and the fact our gene variants directly affect the ability of macrophages to clear bacteria, leave very little doubt that CD centers around innate immunodeficiencies. If you stimulate those macrophages or stimulate autophagy in those macrophages (vit D might stimulate autophagy through NOD2), in theory they would have less issues dealing with bacteria and you wouldn't have a chronically stimulated immune system since those macrophages will stop releasing cytokine that stimulate the immune system.

If you look at crohn's disease from an immunodeficiency angle, a lot of things suddenly make sense, particularly our innate immune system, or primary immune system, whatever people choose to call it.
Kiny you seem to have a good grasp of this topic. If you have some time would you mind reviewing this article and providing some feedback on it? It appears to answer a lot of questions surrounding macrophage dysfunction, and even suggests "A basic abnormality in macrophage biology could also explain extraintestinal manifestations of CD, such as arthritis, and lesions in the eyes, skin, lungs, and other tissues"
07-28-2014, 04:37 PM   #8
Karma
 
Join Date: Mar 2013
xeridea: I'd be interested in Kiny's opinion too. I found the following sentence interesting:

"Our findings of the relationship between bacterial dose and clearance are important in this respect because they demonstrate that CD patients can deal efficiently with small numbers of organisms in the tissues but that the clearance mechanisms are overwhelmed by a large bolus of bacteria."
07-28-2014, 05:07 PM   #9
JMC
Senior Member
 
JMC's Avatar
 
Join Date: Sep 2011
Location: London, United Kingdom
From what I understand the Qubiologics vaccine going on trial in Vancouver is about a treatment that stimulates the macrophages so they can work properly.
Yes, that is my understanding and it is based on a bacteria that is commonly found in the gut, though I cannot find anything on their website specifying which one (though I am lead to believe it is E-coli)


Is the anti-map vaccine working in similar way?
There is a description of the MAP vaccine here: http://crohnsmapvaccine.com/vaccine/, a more technical description is available in this paper: http://www.ncbi.nlm.nih.gov/pubmed/?...ratuberculosis.

The up-coming paper on the vaccine trial in cattle (submitted, awaiting publication) will no doubt contain more details.
07-28-2014, 05:13 PM   #10
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
Thank you. I have linked that study a few times on the forum. It is why I argued many times with Xiaofa Qin that a clear differentiation needs to be made between UC and Crohn's disease. UC patients don't suffer from lack of pro-inflammatory cytokine release from macrophages and have normal neutrophil recruitment, they also don't have variants in genes related to autophagy. UC patients suffer from indiscriminate inflammation of the colon, which to many indicates that the antigen in UC is a self organ and autoimmunity. Crohn's disease and UC are very different diseases and a clear distinction between the two needs to be made if we ever want to solve either one.

A lot of focus and attention has been spent on the adaptive immune response, it's implicated in AIDS and other immunodeficiency diseases. Very little attention has been spent on immunodeficiency related to the innate immune system.

I find MAP in crohn's disease interesting to discuss. But the innate immune response is nonspecific compared to the adapative immune response. Specific immune responses are the job of lymphocytes and their cytotoxic ability to kill bacteria, I think we should consider MAP, but be careful not to put all hope on MAP, because an innate immunodeficiency of macrophages would probably result in many bacteria exploiting those deficiences. MAP and like the article mentions AIEC, just happen to be good candidates, because they're perfect candidates to exploit macrophage deficiencies.
07-28-2014, 05:47 PM   #11
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
"A basic abnormality in macrophage biology could also explain extraintestinal manifestations of CD, such as arthritis, and lesions in the eyes, skin, lungs, and other tissues"
yes, it would just manifest itself most in the intestine, because of the high concentration of macrophages and peyer's patches there, all other manifestations of the disease would be secondary to what happens in the intestine

peyer's patches and therefore macrophages being most active in teenage years would actually explain why most CD patients are teenagers during disease onset

we have many of the pieces of the puzzle
07-28-2014, 06:25 PM   #12
xeridea
Senior Member
 
xeridea's Avatar
I find MAP in crohn's disease interesting to discuss. But the innate immune response is nonspecific compared to the adapative immune response. Specific immune responses are the job of lymphocytes and their cytotoxic ability to kill bacteria, I think we should consider MAP, but be careful not to put all hope on MAP, because an innate immunodeficiency of macrophages would probably result in many bacteria exploiting those deficiences. MAP and like the article mentions AIEC, just happen to be good candidates, because they're perfect candidates to exploit macrophage deficiencies.
And for those following the SSI Trial, their vaccine target is in fact a proprietary strain of AIEC (Adherent Invasive E. Coli).
07-28-2014, 11:16 PM   #13
Lady Organic
Forum Monitor
 
Lady Organic's Avatar
And for those following the SSI Trial, their vaccine target is in fact a proprietary strain of AIEC (Adherent Invasive E. Coli).
is there an antibiotic in the SSI vaccine just like in the MAP vaccine?
07-29-2014, 03:22 AM   #14
worriedboy
Senior Member
 
Join Date: Mar 2011

My Support Groups:
1. I am wondering, what do you guys think that a "remission" actually is ?

It has been in my mind for a while, and if the persistent infecion of MAP/AIEC (or other intracellular mycobacteria) is not cleared - then how the chronic inflammation my suddenly stop ? (either spontaneously or after a course of medication) .

I am almost sure that my Crohns onset began due to a severe infection - this is not rare, I read. I wonder when MAP and AIEC tests will be more accessible, I am really curious what we the result show.

2. Have you guys noticed that Redhill Bio also got RHB104 trials for RA and MS ? Do you believe that those could be results of infections as well ?
Or maybe, we should differentiate between cases in which those are "secondary" (to Crohns for example) to "primary" where they are a standalone issue ?
07-29-2014, 03:33 AM   #15
JMC
Senior Member
 
JMC's Avatar
 
Join Date: Sep 2011
Location: London, United Kingdom
is there an antibiotic in the SSI vaccine just like in the MAP vaccine?
There isn't an antibiotic in the MAP vaccine, but there are antibiotics against MAP

07-29-2014, 08:18 AM   #16
xeridea
Senior Member
 
xeridea's Avatar
is there an antibiotic in the SSI vaccine just like in the MAP vaccine?
My understanding is that the SSI vaccine is based on a killed strain of a proprietary [Adherent Invasive] E. Coli bacteria. Think flu shot. I would think the mechanism by which it works is it trains the adaptive immune system to recognize this (and similar?) bacteria and stage a secondary defense against it where the innate immune system falls short.

The MAP vaccine would similarly recruit the adaptive immune system to recognize and help fight it off. What I'm curious about is that since MAP is an intracellular infection (lives inside host cell) would the MAP vaccine work to clear the infection by itself, or if the treatment would required antibiotics to first clear it, and then the vaccine would help prevent re-infection.
07-29-2014, 05:04 PM   #17
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
You could target AIEC with Hydroxychloroquine, intracellular AIEC is extremely vulnerable to changes in pH, there are some crohn's disease trials where they are using cipro together with Hydroxychloroquine. It's used to kill malaria too. Hopefully there is some better treatment soon.
07-29-2014, 07:42 PM   #18
Lady Organic
Forum Monitor
 
Lady Organic's Avatar
You could target AIEC with Hydroxychloroquine, intracellular AIEC is extremely vulnerable to changes in pH, there are some crohn's disease trials where they are using cipro together with Hydroxychloroquine. It's used to kill malaria too. Hopefully there is some better treatment soon.
yes, I have come across that trial. Plaquenil is widely used in psoriasis and RA and often in combinaition with methotrexate, but I think the reason why its not being used in IBD is for the increased risk of diearrhea with this treatment, but im not sure.
Reply

Crohn's Disease Forum » Books, Multimedia, Research & News » Infliximab modifies response to MAP infection
Thread Tools


All times are GMT -5. The time now is 03:02 PM.
Copyright 2006-2017 Crohnsforum.com