Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: the diagnostic significance of interleukin-18 and interleukin-6

Cytokine. 2012 May;58(2):287-94. doi: 10.1016/j.cyto.2012.02.006. Epub 2012 Mar 6.


Macrophage-activation syndrome (MAS) is a potentially life-threatening complication of systemic juvenile idiopathic arthritis (s-JIA). Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, is an effective cytokine inhibitor for the treatment of s-JIA. We described the clinical courses of five cases of MAS during TCZ therapy and demonstrated the need for monitoring serum interleukin (IL)-18 and IL-6 concentrations. Clinical symptoms of patients with s-JIA receiving TCZ were apparently mild compared to those not receiving TCZ. Furthermore, serum CRP concentrations never increased during TCZ therapy, even in MAS. Serum IL-6 concentrations increased during s-JIA flare-up and with the complication of infection. Serum IL-18 concentrations increased persistently before the other measures of disease activity. The clinical symptoms of MAS and s-JIA could be masked during TCZ therapy; hence, monitoring serum concentrations of IL-18 and IL-6 is recommended for the evaluation of disease activity in s-JIA and to detect the complication of infection.

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Arthritis / drug therapy*
  • Arthritis / immunology
  • Child
  • Female
  • Humans
  • Macrophage Activation / drug effects*
  • Male


  • Antibodies, Monoclonal, Humanized
  • tocilizumab