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The article analyzes possible relationship between biologic therapies for chronic plaque psoriasis (CPP) and major adverse cardiovascular events (MACE). As reported, the monoclonal antibodies ustekinumab and briakinumab have been proven to be effective in treating CPP, but reports have emerged that MACE have occurred among patients given with anti-interleukin (IL) 12/23 agents. Study findings reveal that no significant difference was found in terms of MACE rates between patients receiving anti-IL 12/23 antibodies and those receiving placebo treatment.

Objective: To determine whether 312-nm UV-B alters production of effector and regulatory cytokines by viable T cells that remain in psoriatic lesions during UV-B phototherapy. Design: Prospective study. Setting: General clinical research center of The Rocke-feller University Hospital. Patients: Ten adult patients with moderate to severe psoriasis vulgaris that was difficult to manage were sequentially enrolled in our protocols, and biopsies were taken at various time points from resolving lesions. Intervention: Narrowband (312-nm) UV-B was given starting at 50% of a minimum erythema dose, then increased daily 10% to 15% if no apparent erythema was induced. Patients continued with treatment until maximal benefit was noted. In some experiments, T cells were irradiated ex vivo with standard TL-01 fluorescent bulbs (Philips Lighting Co, Somerset, NJ). Main Outcome Measures: Intracellular cytokine staining was done using flow cytometry to quantify numbers of cytokine-producing cells from epidermal and peripheral T cells. The production of messenger RNA for interleukin (IL) 12, interferon (IFN) γ, tumor necrosis factor α, IL-4, and IL-10 was measured by quantitative reverse transcription-polymerase chain reaction. Results: Ultraviolet-B treatment eliminated production of IL-12 messenger RNA and decreased production of IFN-γ messenger RNA by more than 60% in irradiated psoriasis lesions (P<.03 for both). Within 1 to 2 weeks of starting UV-B treatment, the frequency of viable T cells producing IFN-γ decreased 40% to 65%. In contrast, mRNA for IL-4 increased by 82% (P=.05) during UV-B treatment, and the number of IL-4-producing cells increased by 228% after 1 week of treatment. In vitro experiments established that, on the single-cell level, survival and cytokine production by type 1 T cells were differentially regulated by UV-B. Conclusions: Therapeutic UV-B suppresses the type 1 (proinflammatory) axis as defined by IL-12, IFN-γ,... [ABSTRACT FROM AUTHOR]

Background: Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action. Observations: Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore, following TMP bath PUVA therapy, the numbers of epidermal CD1a+ Langerhans cells were markedly reduced, and CD86+ cells were eliminated. Through in vitro assays, TMP was found to be about 10 000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes. Conclusions: Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin. [ABSTRACT FROM AUTHOR]