Why Cetirizine may work

[nograde]

(As a new user I cannot post links, so excuse the odd citation references. Google gives you immediate results though.-9

Short summary:


* Ceterizine _may_ lower PGD2 levels (only one old study, other studies contradict)

... prostaglandin D2 (PGD2) production, which peaked at 3 to 5 hours, was clearly reduced by cetirizine treatment, being lower at all time points during the reaction ... The inhibition was most marked during the fifth hour of the reaction when there was a 50% suppression of the PGD2 level by cetirizine.
Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction. -- 1989

* Ceterizine _may_ enhance PGE2 levels (only one study)

Cetirizine (0.1-10 micrograms/ml) enhanced PGE2 release by resting human monocytes ... Our findings point to an anti-inflammatory action of cetirizine via PGE2 release and histamine H2 interactions.
In vitro effect of cetirizine on PGE2 release by rat peritoneal macrophages and human monocytes. -- 1994

* Cetirizine definitely prevents harmful downstream effects of PGD2

I think the last point is the best way to explain the purported results by using cetirizine topically. Remember that PGD2 acts on two receptors DP1 (a.k.a PTGDR) and DP2 (a.k.a. GPR44, CRTH2). Cotsarelis showed that DP2 is the culprit in male pattern baldness. DP1 and DP2 may even have opposing roles:

DP1-mediated signaling has been attributed to increased vasodilation, increased inflammatory cell survival, and increased inflammatory cell extravasation into allergic sites. These actions dovetail with the pro-inflammatory activity resulting from CRTH2/DP2 stimulation, which has been shown to mediate chemotaxis of inflammatory cells, to enhance cytokine and cell adhesion molecule expression, and to increase Th2 lymphocyte and eosinophil cell accumulation. Conversely, DP1-mediated signaling decreases eosinphilia, airway hyper-responsiveness, dendritic cell chemotaxis, IL-12 synthesis, T-cell activation, and cytokine (IFN-γ and IL-2) synthesis, all of which serve to dampen inflammation.
The Hematopoietic PGD2 Synthase Pathway: Synchronizing the inflammatory response and its resolution

But note the actions of DP2 activation (the cause of male pattern baldness)

CRTH2: This gene encodes a G-protein-coupled receptor that is preferentially expressed in CD4+ effector T helper 2 (Th2) cells. This protein is a prostaglandin D2 receptor that mediates the pro-inflammatory chemotaxis of eosinophils, basophils, and Th2 lymphocytes generated during allergic inflammation.
NCBI Gene ID: 11251

And here a list of studies showing the effects of Cetirizine all counteracting of the effects of DP2 activation (note that Cetirizine seems to have much more effects than simply inhibiting H1 receptor):

Intraperitoneal pretreatment with cetirizine inhibited eosinophilia induced by either PAF (ED50 = 19 mg kg-1) or compound 48/80 (ED50 = 14 mg kg-1) whereas meclizine, another histamine H1-receptor antagonist, was inactive.
Interference of cetirizine with the late eosinophil accumulation induced by either PAF or compound 48/80. – 1992

In allergic subjects, superoxide anion generation 60 min after platelet-activating factor (PAF) activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1 μg … PAF-induced eosinophil chemotaxis was also inhibited by cetirizine … These results suggest cetirizine has effects on eosinophils which can not be explained by H1-blockade alone.
Effect of Cetirizine on Human Eosinophil Superoxide Generation, Eosinophil Chemotaxis and Eosinophil Peroxidase in vitro – 1994

Cetirizine significantly reduced eosinophil vacuolisation at all observation periods, i. e. 2, 6, 10 and 24 h, and also inhibited basophil accumulation significantly at 10 h (75% reduction)
Effect of cetirizine, ketotifen and chlorpheniramine on the dynamics of the cutaneous hypersensitivity reaction: a comparative study -- 1992

The in vivo inhibitory effect of a new antiallergic, anti-H1 drug, cetirizine, on eosinophil attraction at skin sites challenged with various stimuli has been recently suggested. In the present work, we confirmed that this molecule, at therapeutical concentration, has a potent inhibitory action on eosinophil response to different chemoattractant mediators.
Inhibition of eosinophil chemotaxis by a new antiallergic compound (cetirizine) – 1988

After the challenge, an evaluation of time-course cutaneous eosinophil infiltrations by a skin window technique was performed. Cetirizine pretreatment reduced skin wheal and erythema elicited by allergen and PAF, 400 and 40 ng, by 74.6% (p less than 0.001), 53.9% (p less than 0.001), and 47% (p less than 0.01), respectively. Skin reactivity induced by PAF-acether was also significantly reduced by cetirizine in nonallergic subjects. Cetirizine reduced at hour 24 eosinophil infiltrations induced by allergen and PAF...This inhibitory effect of cetirizine on allergen and PAF-induced eosinophil infiltration was already effective 2 hours after the challenge... In conclusion, cetirizine inhibited both the immediate cutaneous response and the eosinophil influx induced by allergen and by a potent eosinophil chemotactic factor, such as PAF-acether. Therefore, cetirizine, besides its anti-H1 effect, has the potential to modulate the allergic inflammatory response.
In vivo effects of cetirizine on cutaneous reactivity and eosinophil migration induced by platelet-activating factor (PAF-acether) in man. – 1990

Compared to placebo, cetirizine significantly decreased the eosinophils attraction at skin sites challenged with grass pollen and compound 48/80.
Inhibitory effect of cetirizine 2HCl on eosinophil migration in vivo. – 1987

Several second-generation antihistamines have documented anti-inflammatory effects which appear independent of H1-receptor blockade. We investigated the inhibitory effect of cetirizine and its active enantiomer levocetirizine on eosinophil transendothelial migration. Pre-incubation of eosinophils with cetirizine or levocetirizine dose-dependently inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l.
Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells. – 2002

Recent studies suggest that several second-generation antihistamines can modulate various inflammatory reactions besides their H(1)-receptor antagonism
Influence of cetirizine and levocetirizine on two cytokines secretion in human airway epithelial cells -- 2008

It was shown that both drugs significantly inhibited basophil histamine release induced by anti-igE or specific allergen.
The effects of a new generation of H1 antihistamines (cetirizine and loratadine) on histamine release and the bronchial response to histamine in atopic patients – 1995

Cetirizine induced a shift in the human Th1/Th2 cytokine balance toward a Th1 type response by increasing IFN-gamma production and augmenting suppressor cytokine release (IL-10). We concluded that apart from its known antihistaminic properties, cetirizine may modulate allergic inflammation while the patients are on regular treatment schedules
The effect of cetirizine on IFN-gamma and IL-10 production in children with allergic rhinitis. -- 2005

Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD)… The expression of VCAM-1 (IL-4/Th2-dependent) … was compared in six patients … The administration of cetirizine significantly reduced the VCAM-1 expression in AD patients at each experimental time.
Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine.

 

[HairOutTheWazoo]

Interesting, this is the first I've heard that it may enhance pge2 too. Could be a double whammy here.

 

[squeegee]

Holy **** nograde.. Give me some times to digest all this! Good ****ing work!!:salut:

 

[odalbak]

Nice research nograde.

 

[LawOfThelema]

nice summary. thanks.