Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition

Abstract

As the current antipsoriatic medications are commonly associated with deleterious side-effects, a determined search for safer agents, which could be used alone or in combination with current antipsoriatic drugs, would be very imperative. Psoriasis is believed to be characterized by a type 1 cytokine pattern; interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are predominantly expressed in this disorder. Nitric oxide, reactive oxygen species, histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are supposed to play roles in the pathogenesis of this disorder. Based on the immunopathogenesis of psoriasis, this paper introduces three novel, potential treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory effects on antigen processing and macrophage/T-cell interaction and also on the release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine, which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio and the production of leukotriene B4; and (iii) allopurinol, which scavenges free radicals, inhibits the production of TNF-alpha, and downregulates the expression of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages, which are involved in antigen presentation and production of the inflammatory response, respectively. Importantly, allopurinol, especially in combination with cyclosporin, has been shown to be effective against experimental autoimmune uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.

Allopurinol in Dermatology

“…[63][64][65]68,69] However, it is a relatively unappreciated treatment in dermatology. Moreover, only a limited number of dermatologic diseases have been treated with allopurinol.…”

“…[63][64][65] Downregulate the expression of intercellular adhesion molecule-1 and P2X7 receptors, which may contribute to the communication between macrophages and lymphocytes at inflammatory sites. [63][64][65] Improve endothelial function. [7] Decrease platelet adhesiveness.…”

“…It is characterized by a cell-mediated immune response resulting in T cells overproducing tumor necrosis factor-a (TNFa), interferon-g, interleukin-1 and interleukin-2. [63][64][65] The ability of allopurinol to scavenge free radicals, to suppress the production of TNFa and to downregulate the expression of intercellular adhesion molecule-1 and purinergic P2X7 receptors suggest promising therapeutic effects in the treatment of psoriasis. [63][64][65] The effectiveness of allopurinol in the treatment of psoriasis has been reported.…”

“…[63][64][65] The ability of allopurinol to scavenge free radicals, to suppress the production of TNFa and to downregulate the expression of intercellular adhesion molecule-1 and purinergic P2X7 receptors suggest promising therapeutic effects in the treatment of psoriasis. [63][64][65] The effectiveness of allopurinol in the treatment of psoriasis has been reported. [53,66] In Russia, a study suggested that allopurinol can be beneficial in treating psoriasis; 63 of 147 patients (42.8%) who had received allopurinol together with other antipsoriatic treatments demonstrated an increase in therapeutic effects compared with 46 of 147 patients (31.3%) who did not receive oral allopurinol.…”

Cannabis in the Treatment of Rheumatic Diseases: Suggestions for a Reasoned Approach

“…An important development has been the recognition and elucidation of the antiinflammatory actions of the endocannabinoid system, and of the role of inflammatory mechanisms in the generation of peripheral pain sensation. Cannabinoids have been shown to act also through CB2, TRPV1, GPR55, and descending fiber 5-HT3 receptors, and to inhibit release of interleukins, tumor necrosis factor-α, nitric oxide, and other proinflammatory factors from macrophages and immune cells, which are involved in the generation of pain in animal models of osteoarthritis 10,11,12 . The variety of different mechanisms through which cannabinoids act to relieve pain and inflammation warrants greater confidence that cannabis therapy may have a useful place in rheumatology, even though there is still work to be done in translating from basic studies to clinical use 13 .…”