title: Effect of inhibition of interleukin-12/23 by ustekinumab on the expression of leptin and leptin receptor in human THP-1 macrophages.
abstract: BACKGROUND
  Leptin, an adipocyte-derived circulating cytokine that signals nutritional status, may play a role in the development of psoriasis and its associated systemic diseases. Patients with psoriasis have significantly decreased serum leptin levels compared with controls.
  
  
  OBJECTIVE
  To investigate the effect of two commonly used anti-psoriatic biologic drugs, adalimumab and ustekinumab, on leptin and leptin receptor expression in human macrophages.
  
  
  METHODS
  THP-1 differentiated macrophages were cultured under the following conditions: (i) untreated control, (ii) adalimumab 5 μg/mL, (iii) ustekinumab 1 μg/mL and (iv) ustekinumab 5 μg/mL. Expression of leptin and leptin receptors were measured using real-time quantitative PCR and immunoblotting techniques.
  
  
  RESULTS
  The presence of either adalimumab or ustekinumab in growth medium significantly upregulated expression of leptin receptor in THP-1 human macrophages to 1.98 ± 0.47 and 2.09 ± 0.24, respectively (n = 3, P < 0.01) vs. 1.12 ± 0.19 for untreated control cells. However, only ustekinumab at a concentration of 5 μg/mL augmented expression of leptin to 1.99 ± 0.56 (n = 3, P < 0.01) vs. control untreated cells.
  
  
  CONCLUSIONS
  Enhanced leptin and leptin receptor expression in macrophages exposed to therapeutic levels of ustekinumab suggest a novel immunomodulatory mechanism for this biologic drug. Further mechanistic studies may yield targeted treatment using the leptin pathway, which could reduce the common obesity-related complications of psoriasis while alleviating symptoms and improving prognosis.
authors.affiliation: Winthrop Research Institute and Division of Rheumatology, Allergy and Immunology, Department of Medicine, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Voloshyna
authors.affiliation: Winthrop Research Institute and Division of Rheumatology, Allergy and Immunology, Department of Medicine, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mounessa
authors.affiliation: Winthrop Research Institute and Division of Rheumatology, Allergy and Immunology, Department of Medicine, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Carsons
authors.affiliation: Winthrop Research Institute and Division of Rheumatology, Allergy and Immunology, Department of Medicine, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Reiss
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003879:Dermatologic Agents / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000037:antagonists & inhibitors*; D020738:Leptin / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy; D054411:Receptors, Leptin / Q000378:metabolism*; D000069549:Ustekinumab / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D003879:Dermatologic Agents; D053759:Interleukin-23; D007378:Interleukins; D020738:Leptin; D054411:Receptors, Leptin; D018664:Interleukin-12; D000069549:Ustekinumab; D000068879:Adalimumab