BACKGROUND: Melioidosis, caused by the gram-negative bacterium Burkholderia 
pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia 
and Northern Australia. The NLRP3 inflammasome and its downstream product 
interleukin-1 beta (IL-1β) have been proposed to play crucial roles in 
melioidosis. In this study, we characterized the role of IL-1β more closely and 
we assessed its therapeutic potential.
METHODS: mRNA expression of inflammasome components was determined in isolated 
leukocytes of 32 healthy controls and 34 patients with sepsis caused by B 
pseudomallei.Wild-type (WT), NLRP3-deficient (Nlrp3), and Asc mice were infected 
with B pseudomallei. In additional experiments, infected WT mice were treated 
with an anti-IL-1β antibody. After 24, 48, and 72 hours (h) mice were sacrificed 
and organs were harvested. Furthermore, survival studies were performed.
RESULTS: Patients with melioidosis exhibited lower mRNA levels of caspase-1, 
NLRP3, and ASC. Bacterial dissemination and organ damage were increased in B 
pseudomallei-infected Nlrp3 and Asc mice, together with a reduced pulmonary cell 
influx. Anti-IL-1β treatment of B pseudomallei challenged mice resulted in 
strongly reduced bacterial counts, organ damage, and pulmonary granulocyte 
influx together with reduced mortality. Postponement of anti-IL-1β treatment for 
24 h postinfection still protected mice during melioidosis.
CONCLUSION: Expression of caspase-1, NLRP3, and ASC is altered in melioidosis 
patients. In mice, both NLRP3 and ASC contribute to the host defense against 
melioidosis. Anti-IL-1β treatment protects mice against B pseudomallei infection 
and might be a novel treatment strategy in melioidosis.