Desloratadine (DL) is a new potent and selective H1 receptor antagonist (AH1) that also acts on inflammatory mediators and NF-kB activity. The aim of our study was to evaluate the involvement of the histamine receptor 1 (H1R) in the anti-inflammatory effects of DL.

The H1R cDNA was cloned by RT-PCR to construct the expression vector pCIH1R. After transfection with pCIH1R, overexpression of the H1R in A549 cells was confirmed by Western blotting and immunocytochemistry. Using reporter gene assays, we evaluated the effect of DL, but also diphenhydramine (DPH), a first generation AH1, cimetidine, an AH2, and thioperamide, an AH3, on NF-kB activity in pCIH1R or mock transfected A549 cells.

Overexpression of the H1R resulted in increased NF-kB basal activity. DL significantly inhibited this basal activity in both mock transfected and pCIH1R transfected A549 cells. This effect was weaker for DPH and not significant for the AH2 and the AH3. Histamine failed to induce NF-kB activity in mock transfected cells but significantly induced this activity in pCIH1R transfected cells. DL inhibited histamine-induced NF-kB activity by 68% (p<0.05) and DPH by 55% (p<0.05), but neither the AH2 nor the AH3 could repress histamine-induced NF-kB activity.

These results suggest that DL can inhibit both basal and histamine-induced NF-kB activity by acting, in the first case, as an inverse agonist at the H1R, and in the second case as a classic H1R antagonist. Thus, the H1R seems to play a major role in the anti-inflammatory effects of DL.