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Antihistamines as Th1/Th2 Immunomodulators.

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Looks like cetirizine (Zyrtec) and fexofenadine (Allegra) may not be the best choices for antihistamines for those wanting to promote a Th1 response.


Inhibition of Cytokine-Induced Expression of T-Cell Cytokines by Antihistamines


MS Ashenager,1 T Grgela,1 Y Aragane,2 A Kawada1

1 Department of Dermatology, Kinki University School of Medicine, Osaka, Japan
2 Department of Dermatology, International Tougenkai Institute for Immunotherapy and Phototherapy of the Skin, Osaka, Japan

J Investig Allergol Clin Immunol 2007; Vol. 17(1): 20-26


Abstract


Objective: To investigate immunomodulatory properties of 4 antihistamines available in Japan.

Method: Isolated peripheral blood T cells from healthy volunteers were preincubated with cetirizine, loratadine, olopatadine, or fexofenadine for 30 minutes and then stimulated with interleukin (IL)-12 or IL-4 to skew immune response towards type 1 or type 2 helper T cells. RNA was extracted 6 hours later and semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was performed using primers for IL-5 and interferon (IFN) γ. Supernatants were collected 24 hours after stimulation, and cytokine production was quantified by enzyme-linked immunosorbent assay (ELISA).

Results: RT-PCR revealed that IL-12–induced expression of IFN-γ was partially suppressed by loratadine and fexofenadine and that all 4 agents tested inhibited IL-4–induced expression of IL-5.

ELISA demonstrated that IL-12–induced IFN-γ production was significantly suppressed by cetirizine and fexofenadine and IL-4–induced IL-5 production was downregulated by three agents with the exception of cetirizine.

This study demonstrates that antihistamines have varying immunomodulatory properties, suggesting treatment choice for atopic dermatitis can be directed by disease signs and symptoms.

Key words: Atopic dermatitis antihistamines. IL-4. IL-12.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Just found a pdf of this paper here.

Three things that come to mind:

1. Interferon-gamma is only high in pwME who have been ill for less than 3 years according to the Hornig/Lipkin cytokine study. It's slightly low after 3 years. So are many other cytokines.
2. @Jonathan Edwards is sceptical about a Th1-Th2 shift, I understand.
3. This study was ex vivo/in vitro, so limited conclusions can be drawn.

Interesting nonetheless.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
1. Interferon-gamma is only high in pwME who have been ill for less than 3 years according to the Hornig/Lipkin cytokine study. It's slightly low after 3 years. So are many other cytokines.

Interferon gamma seems to be an important part of the Th1 response which seems to be consistently lacking in our population. Increasing it (especially if it is low in later stage disease) seems to be helpful for many. I think this is one of the reasons that LDN is useful (along with reducing inflammation in general) and other known Th1 shifters.

But certainly a healthy population may have a differing cytokine response to any agent, including antihistamines.

2. @Jonathan Edwards is sceptical about a Th1-Th2 shift, I understand.

JE seems to be skeptical and dismissive of just about everything to do with anything so far.

To be fair, many doctors are skeptical about the relevance of the Th1/Th2 theory though, and I agree that the seesaw analogy seems overly simplistic.

That said, I think that avoiding things that are known to propagate a Th2 response or to inhibit a Th1 response is probably a reasonable approach for many of us, especially those with viral or intracellular infections.

3. This study was ex vivo/in vitro, so limited conclusions can be drawn.

True. More research is needed to draw any conclusions. I just thought it was interesting that antihistamines, along with antivirals and antibiotics are all immunomodulatory. Just goes to show how little we know about how all these medicines really work in our body for the most part.

And, many people take antihistamines so between this and the recent Lyme/Claritin link, it's looking like loratadine may be a better choice considering the limited information at hand.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
JE seems to be skeptical and dismissive of just about everything to do with anything so far.

That has certainly not been my experience. I think that you are doing Prof Edwards a great disservice, but I am sure he will cope!