OBJECTIVES: To define in patients affected by familial Mediterranean fever (FMF) 
whether or not interleukin (IL)-1β secretion (1) is enhanced, (2) correlates 
with the type of MEFV mutation and (3) is mediated by NLRP3.
METHODS: Freshly isolated monocytes from 21 patients with FMF (12 homozygous and 
9 heterozygous), 14 MEFV healthy carriers and 30 healthy donors (HDs), 
unstimulated or after lipopolysaccharide (LPS)-induced activation, were analysed 
for redox state (production of reactive oxygen species (ROS) and antioxidant 
responses) and IL-1β and IL-1 receptor antagonist (IL-1Ra) secretion. NLRP3 
down-modulation was induced by in vitro silencing of the NLRP3 gene.
RESULTS: LPS-stimulated monocytes from patients with FMF displayed enhanced 
IL-1β secretion, which correlated with number and penetrance of MEFV mutations. 
Silencing of NLRP3 consistently inhibited IL-1β secretion. As in other 
autoinflammatory diseases, FMF monocytes produced more ROS than genetically 
negative cells from HDs. Unlike in cryopyrin-associated periodic fever syndromes 
(CAPS), however, they were characterised by a conserved and sustained 
antioxidant response. Consistent with this finding, activated MEFV-mutated 
monocytes did not exhibit the functional indicators of oxidative stress observed 
in CAPS, including accelerated IL-1β secretion and deficient production of 
IL-1Ra.
CONCLUSIONS: MEFV-mutated monocytes display enhanced IL-1β secretion, which 
correlates with number of high-penetrance mutations and level of endogenous ROS. 
Unlike NLRP3-mutated cells, monocytes carrying MEFV mutations withstand 
oxidative stress and preserve IL-1Ra production, thereby limiting inflammation. 
Finally, in contrast with that found in the animal model, the increased 
secretion of IL-1β by LPS-stimulated FMF monocytes is NLRP3-dependent.