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07 January 2020 : Clinical Research  

Indirect Regulation and Equilibrium of p35 and p40 Subunits of Interleukin (IL)-12/23 by Ustekinumab in Psoriasis Treatment

Jiong Zhou1ABFG, Ji-Yang Shen2CDEF, Lun-Fei Liu13AB, Ji-Su Chen1AB, Ting-Ting Dou4BC, Min Zheng1BG, Sui-Qing Cai1ABG*

DOI: 10.12659/MSM.920371

Med Sci Monit 2020; 26:e920371

Abstract

BACKGROUND: Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms.

MATERIAL AND METHODS: Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment).

RESULTS: Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection.

CONCLUSIONS: We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.

Keywords: Antibodies, Monoclonal, Interleukin-12 Subunit p35, Interleukin-12 Subunit p40, Psoriasis, Dermatologic Agents, Double-Blind Method, RNA, Messenger, Severity of Illness Index, Ustekinumab

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750