title: Mouse model of mevalonate kinase deficiency: comparison of cytokine and chemokine profile with that of human patients.
abstract: BACKGROUND
  Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disease caused by blocking of the enzyme mevalonate kinase in the pathway of cholesterol and isoprenoids. The pathogenic mechanism originating an immune response in MKD patients has not been clearly understood.
  
  
  METHODS
  We investigated the dysregulation of expression of selected cytokines and chemokines in the serum of MKD patients. The results have been compared with those observed in an MKD mouse model obtained by treating the mice with aminobisphosphonate, a molecule that is able to inhibit the cholesterol pathway, mimicking the genetic block characteristic of the disease.
  
  
  RESULTS
  Interleukin (IL)-1β, IL-5, IL-6, IL-9, IL-17, granulocyte colony-stimulating factor, monocyte chemotactic protein-1, tumor necrosis factor-α, and IL-4 expression were dysregulated in sera from MKD patients and mice. Moreover, geraniol, an exogenous isoprenoid, when administered to MKD mice, restored cytokines and chemokines levels with values similar to those of untreated mice.
  
  
  CONCLUSIONS
  Our findings, which were obtained in patients and a mouse model mimicking the human disease, suggest that these cytokines and chemokines could be MKD specific and that isoprenoids could be considered as potential therapeutic molecules. The mouse model, even if with some limitations, was robust and suitable for routine testing of potential MKD drugs.
authors.affiliation: Health Genetics Unit, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy. annalisa.marcuzzi@burlo.trieste.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marcuzzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Zanin
authors.forename: Giulio
authors.initials: G
authors.lastname: Kleiner
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monasta
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004164:Diphosphonates / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D054078:Mevalonate Kinase Deficiency / Q000276:immunology*; D051379:Mice; D013045:Species Specificity; D013729:Terpenes
chemical_list: D000080462:Acyclic Monoterpenes; D018925:Chemokines; D016207:Cytokines; D004164:Diphosphonates; D013729:Terpenes; C007836:geraniol