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Crohn's Disease Forum » Books, Multimedia, Research & News » Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection


10-25-2014, 03:43 PM   #1
kiny
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Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

http://onlinelibrary.wiley.com/doi/1...34B065C.f02t03

Infliximab therapy increases the frequency of circulating CD16+ monocytes and modifies macrophage cytokine response to bacterial infection

2014 Sep

Nazareth, Magro F, Silva J, Duro M, Gracio D, Coelho R, Appelberg R, Macedo G, Sarmento A

University Fernando Pessoa, Porto, Portugal

Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab.

Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points.

To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16+ and CD16− monocytes and the frequency of TNF+ cells among CD16+ and CD16− monocyte-derived macrophages from CD patients.

Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria.

An infliximab-dependent increase in the frequency of circulating CD16+ monocytes (particularly the CD14++CD16+ subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%).

In response to MAP infection, macrophages obtained from CD16+ monocytes were higher TNF producers and CD16+ macrophages from infliximab-treated CD patients showed increased frequency of TNF+ cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16+ circulating monocytes, particularly of the CD14++CD16+ subset.

Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages.
10-25-2014, 06:15 PM   #2
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Not entirely sure what this is saying but assuming it's saying it stimulates macrophages?
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10-25-2014, 07:29 PM   #3
kiny
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monocytes and macrophages are 1 of the 3phagocytes of the innate immune system (granulocytes and dendritic cells are the other 2)

macrophages are just mature monocytes, that went from blood into tissue (they live quite a long time, well, compared to other immune cels)

they line all the intestine, and they're part of the innate immune system, they react against bacteria, can think of them literally eating and destroying bacteria, they also have another function as a signaler together with dendritic cells, they can set off the adaptive immune system

CD(number) is usually just a way to differentiate types of immune cells depending on type of molecules on the surface of the cell, you can categorise not just macrophages but other cells too like that

what the study is saying is that if you give a person infliximab you increase the number of circulating CD16 monocytes (they're like macrophages but immature and only in blood) and increase the TNF-alpha release from CD16 macrophages (they're the mature ones that are in tissue, the intestine is full of them) against bacteria like E Coli and MAP

I have said many times in the past that I think infliximab has an antibacterial function in CD patients.
10-25-2014, 08:05 PM   #4
kiny
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In the crohn's disease studies, like this one, they also often say "circulating monocytes" or "blood monocytes". It's not to differentiate between macrophages and monocytes, it's because the majority of monocytes don't circulate, they're in the spleen taking a nap until they're called upon during wound healing / infections etc, the spleen is kind of like their house to sleep in. Only a minority (a third or so), is constantly patrolling blood.
10-25-2014, 08:09 PM   #5
rollinstone
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Why don't they include macrophage penetrating antibiotics with remicade, maybe that'd garner higher efficiency
10-25-2014, 08:12 PM   #6
kiny
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Why don't they include macrophage penetrating antibiotics with remicade, maybe that'd garner higher efficiency
It's been suggested by some.
10-26-2014, 04:17 AM   #7
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It's an interesting paper, and I mentioned it when it was first published as I believe it is yet more evidence that Infliximab can kill MAP infection :-)
10-26-2014, 07:34 AM   #8
mf15
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I am sort of on the same trail,where most of the IBD meds enhance the immune response against MAP,or inhibit growth. If fact there is a pretty good story that since about 1942 the GI medical community has unknowingly been modulating MAP infection with all the meds that work on IBD.
Anyhow this paper might confound things a bit. Where biologics are increasing the incidence of NTM
none TB mycobacteria infections in RA and other patients.
Old Mike
http://wwwnc.cdc.gov/eid/article/15/10/09-0310_article

To go along with Kiny's paper.
http://www.pulsus.com/cddw2010/abs/114.htm

Last edited by mf15; 10-26-2014 at 08:02 AM.
10-26-2014, 09:33 AM   #9
JMC
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Anyhow this paper might confound things a bit. Where biologics are increasing the incidence of NTM
none TB mycobacteria infections in RA and other patients.
Old Mike
http://wwwnc.cdc.gov/eid/article/15/10/09-0310_article
Are biologics increasing the incidence of NTM or are people who are genetically prone to mycobacterial infections taking anti–TNF-α medication?
10-26-2014, 10:31 AM   #10
mf15
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JCM I have no idea.
But just ran across this, cigarettes are loaded with MAP.
http://www.ncbi.nlm.nih.gov/pmc/arti...pdf/332757.pdf
Old Mike
10-26-2014, 11:06 AM   #11
JMC
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JCM I have no idea.
But just ran across this, cigarettes are loaded with MAP.
http://www.ncbi.nlm.nih.gov/pmc/arti...pdf/332757.pdf
Old Mike
Well, I have wondered before whether the reason why smoking has such a negative impact on Crohn's was that it caused people to inhale MAP and that paper suggests it is a possible mechanism
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