Vitamin D3 derivatives, alone or in combination with glucocorticoids, suppress streptococcal pyrogenic enterotoxin A‐stimulated proliferation of peripheral blood mononuclear cells in patients with psoriasis

Abstract

Bacterial colonization on skin or tonsil may influence the clinical response of patients with psoriasis to immunosuppressive drugs. However, few studies have investigated the effects of bacterial superantigens on therapy in these patients. Recently, combination therapy with topical glucocorticoids (GC) and vitamin D3 (VD3) appears to be more effective than GC or VD3 monotherapy for psoriasis. We evaluated the suppressive effects of betamethasone butyrate propionate (BBP), three VD3 derivatives (calcipotriol, maxacalcitol and tacalcitol), cyclosporin and BBP plus VD3, on concanavalin A (ConA)-or streptococcal pyrogenic enterotoxin A (SPEA)-stimulated proliferation of peripheral blood mononuclear cells (PBMC) obtained from 35 psoriasis patients. Drug concentrations effecting 50% inhibition concentration of ConA-or SPEA-stimulated PBMC proliferation were estimated. Cytokine levels of tumor necrosis factor-a, c-interferon, interleukin-1b, -2, -4, -5, -6, -8 -10 and -12p70 in PBMC culture supernatants were measured with bead-array procedures. Suppression of PBMC proliferation by BBP was significantly lower when PBMC were stimulated by SPEA than when stimulated by ConA. In contrast, the suppressive effects of calcipotriol and tacalcitol increased significantly when PBMC were stimulated by SPEA than when stimulated by ConA. The suppressive effect of BBP on SPEA-stimulated PBMC proliferation was improved significantly by adding 1-1000 ng/mL calcipotriol, compared with BBP alone. Cytokine levels in PBMC culture supernatants were not significantly different between ConA-and SPEA-stimulated PBMC. Calcipotriol and BBP in combination markedly suppressed SPEA-stimulated PBMC proliferation. SPEA produced by colonization of hemolytic streptococci may reduce the efficacy of BBP but not VD3 derivatives in the treatment of psoriasis.

The CCL20 and CCR6 axis in psoriasis

“…In addition, the CCL20/CCR6 chemotactic system is critically involved in the maintenance of the TNF‐α/IL‐23/IL‐17A axis. Therapeutic agents for psoriasis include topical steroids, topical vitamin D3 derivatives, phototherapy, phosphodiesterase‐4 inhibitors, cyclosporine, methotrexate and biologics targeting TNF‐α, IL‐23 and IL‐17A . As the TNF‐α/IL‐23/IL‐17A axis plays a pivotal role in the pathogenesis of psoriasis, the efficacy of anti–TNF‐α/IL‐23/IL‐17A biologics is excellent …”

“…Therapeutic agents for psoriasis include topical steroids, topical vitamin D3 derivatives, phototherapy, phosphodiesterase-4 inhibitors, cyclosporine, methotrexate and biologics targeting TNF-α, IL-23 and IL-17A. [38][39][40][41][42][43][44][45][46] As the TNF-α/IL-23/IL-17A axis plays a pivotal role in the pathogenesis of psoriasis, the efficacy of anti-TNF-α/IL-23/IL-17A biologics is excellent. 3,24,46 In this review, we will summarize the current research topics regarding the CCL20/CCR6 axis in psoriasis.…”

Autoimmunity and autoimmune co‐morbidities in psoriasis

“…The accelerated TNF‐ α /IL‐23/IL‐17 axis coincides with the characteristic histopathology of psoriasis, such as epidermal hyperproliferation, aberrant differentiation and neutrophilic microabscess. Regarding treatments, topical application of steroids and vitamin D3 analogues inhibits psoriatic inflammation and normalizes epidermal differentiation . Systemic treatments, such as cyclosporine, methotrexate and the phosphodiesterase 4 inhibitor apremilast, are useful for patients with extensive lesions .…”

“…Regarding treatments, topical application of steroids and vitamin D3 analogues inhibits psoriatic inflammation and normalizes epidermal differentiation. [61][62][63][64][65] Systemic treatments, such as cyclosporine, methotrexate and the phosphodiesterase 4 inhibitor apremilast, are useful for patients with extensive lesions. [66][67][68] Clinical trials have demonstrated the efficacy of the oral janus kinase inhibitor tofacitinib for psoriasis.…”

The contribution of IL-17 to the development of autoimmunity in psoriasis

“…[6][7][8][9][10] Therapeutic modalities for psoriasis include topical steroids, topical vitamin D3 derivatives, phototherapy, phosphodiesterase-4 inhibitors, cyclosporine, methotrexate, and biologics targeting TNF-a, IL-23, and IL-17A. [11][12][13][14][15][16][17][18][19] The excellent therapeutic efficacy of anti-TNF-a/IL-23/IL-17A biologics for psoriasis point to a central role of the TNF-a/IL-23/IL-17A axis in its pathogenesis. 20,21 Additionally, genetic and environmental factors are known to be involved in its pathogenesis.…”