TNF-alpha compensates for the impaired host defense of IL-1 type I receptor-deficient mice during pneumococcal pneumonia

To determine the role of IL-1 in the host defense against pneumonia, IL-1R type I-deficient (IL-1R(-/-)) and wild-type (Wt) mice were intranasally ino culated with Streptococcus pneumoniae. Pneumonia resulted in elevated IL-1 alpha and IL-1 beta mRNA and protein levels in the lungs. Survival rates di d not differ between IL-1R(-/-) and Wt mice after inoculation with 5 x 10(4 ) or 2 x 10(5) CFU. At early time points (24 and 48 h) IL-1R(-/-) mice had 2-log more S. pneumoniae CFU in lungs than Wt mice; at 72 h bacterial outgr owth in lungs was similar in both groups. Upon histopathologic examination IL-1R(-/-) mice displayed a reduced capacity to form inflammatory infiltrat es at 24 h after the induction of pneumonia. IL-1R(-/-) mice also had signi ficantly less granulocyte influx in bronchoalveolar lavage fluid at 24 h af ter inoculation. Since TNF is known to enhance host defense during pneumoni a, we determined the role of endogenous TNF in the early impairment and sub sequent recovery of defense mechanisms in IL-1R(-/-) mice. All IL-1R(-/-) m ice treated with anti-TNF rapidly died (no survivors (of 14 mice) after 4 d ays), while 10-day survival in IL-1R(-/-) mice (control Ab), Wt mice (anti- TNF), and Wt mice (control Ab) was 7 of 13, 3 of 14, and 12 of 13, respecti vely. These data suggest that TNF is more important for host defense agains t pneumococcal pneumonia than IL-1, and that the impaired early host defens e in IL-1R(-/-) mice is compensated for by TNF at a later phase.