- The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1a 2/2 , IL-1b 2/2 , IL-1a/b 2/2 and IL-1R antagonist (IL-1Ra) 2/2 mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1b 2/2 and IL-1a/b 2/2 mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1a 2/2 and IL-1Ra 2/2 mice. Treatment of IL-1b 2/2 mice with rIL-1b significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1a 2/2 and IL-1Ra 2/2 but not in IL-1b 2/2 and IL-1a/b 2/2 mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1a 2/2 and control mice. However, S. pneumoniae-infected IL-1b 2/2 , IL-1a/b 2/2 and IL-1Ra 2/2 mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1a and IL-1b in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1b has a major role in resistance to primary pneumococcal infection while the role of IL-1a is less important.