Histamine 2 Receptor Agonism and Histamine 4 Receptor Antagonism Ameliorate Inflammation in a Model of Psoriasis
Kristine Rossbach, Katharina Wahle, Gustav Bruer, Ralph Brehm, Marion Langeheine, Kristina Rode, Katrin Schaper-Gerhardt, Ralf Gutzmer, Thomas Werfel, Manfred Kietzmann, Wolfgang Bäumer
Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferative keratinocytes and immune cell infiltration into the skin, often accompanied by itch. Histamine, acting via histamine 1–4 receptors, is known to modulate immune responses in the skin and to induce itch. The aim of this study was to test the role of histamine 2 receptors and histamine 4 receptors in the imiquimod-induced psoriasis-like skin inflammation model. BALB/c mice were treated intraperitoneally with amthamine (histamine 2 receptor agonist), JNJ-39758979 (histamine 4 receptor antagonist), a combination of both, or vehicle twice daily in a preventive manner. Imiquimod was applied once daily onto the back skin for 10 consecutive days. Stimulation of histamine 2 receptors and blockade of histamine 4 receptors ameliorated imiquimod-induced skin inflammation. The combination of amthamine and JNJ-39758979 reduced skin inflammation even more pronounced, diminished epidermal hyperproliferation, and inhibited spontaneous scratching behaviour. A combination of histamine 2 receptor agonist and histamine 4 receptor antagonists could represent a new strategy for the treatment of psoriasis.
Psoriasis is characterized by hyperproliferative keratinocytes and immune cell infiltration. Histamine has pro-inflammatory properties; it stimulates the proliferation of keratinocytes, and the histamine concentration in skin is increased in psoriatic lesions. However, classical antihistamines (histamine 1 receptor antagonists) play only a minor role in therapy for psoriasis. This study reveals that treatment with histamine 2 receptor agonists, and blockade of the histamine 4 receptor ameliorates inflammation in a mouse model of psoriasis and diminishes psoriasis-associated itch. Histamine 2 receptor agonists and histamine 4 receptor antagonists might thus be new targets to treat psoriasis.