In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes.

J Exp Med 2009 May 13;206(5):1029-36. Epub 2009 Apr 13.

National Amyloidosis Centre, Royal Free and University College Medical School, London NW3 2PF, England, UK.

The investigation of interleukin 1beta (IL-1beta) in human inflammatory diseases is hampered by the fact that it is virtually undetectable in human plasma. We demonstrate that by administering the anti-human IL-1beta antibody canakinumab (ACZ885) to humans, the resulting formation of IL-1beta-antibody complexes allowed the detection of in vivo-produced IL-1beta. A two-compartment mathematical model was generated that predicted a constitutive production rate of 6 ng/d IL-1beta in healthy subjects. In contrast, patients with cryopyrin-associated periodic syndromes (CAPS), a rare monogenetic disease driven by uncontrolled caspase-1 activity and IL-1 production, produced a mean of 31 ng/d. Treatment with canakinumab not only induced long-lasting complete clinical response but also reduced the production rate of IL-1beta to normal levels within 8 wk of treatment, suggesting that IL-1beta production in these patients was mainly IL-1beta driven. The model further indicated that IL-1beta is the only cytokine driving disease severity and duration of response to canakinumab. A correction for natural IL-1 antagonists was not required to fit the data. Together, the study allowed new insights into the production and regulation of IL-1beta in man. It also indicated that CAPS is entirely mediated by IL-1beta and that canakinumab treatment restores physiological IL-1beta production.

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http://dx.doi.org/10.1084/jem.20082481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715040PMC
May 2009
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References

(Supplied by CrossRef)
The IL-1 family and inflammatory diseases
Dinarello et al.
Clin. Exp. Rheumatol. 2002
A recently recognised chronic inflammatory disease of early onset characterised by the triad of rash, central nervous system involvement and arthropathy
Prieur et al.
Clin. Exp. Rheumatol. 2001

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