Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1

Natural and synthetic immunomodulators that increase nonspecific resistance to infection are also known to induce interleukin 1 (IL 1) production. Previous studies have demonstrated a protective effect of recombinant human IL 1 beta against death from infection caused by Pseudomonas aeruginosa. In the present study we investigated the effect of IL 1 beta or IL 1 alpha on the survival of neutropenic mice with a lethal Candida albicans infection. Mice with cyclophosphamide-induced neutropenia were injected with 3 X 10(5) C. albicans i.v. When 80 ng IL 1 beta was given as a single i.p. injection 24 h before the infection, survival compared to that in control animals was as follows: 100% vs. 97% at 24 h, 83% vs. 70% at 48 h and 70% vs. 23% at 72 h after the infection (p less than 0.01). The effect of IL 1 was also apparent when it was given 1/2 h before or 6 h after the infection. The results obtained with 80 ng IL 1 alpha given at 24 h before infection were similar to that obtained with IL 1 beta. The numbers of Candida cultured from the blood, liver, spleen, and kidney were not significantly different in IL 1 beta-treated and control animals. Passive transfer of serum obtained from mice pretreated with IL 1 to recipient mice did not provide protection against a subsequent lethal candidal infection. In conclusion, the present study demonstrates that IL 1 beta and IL 1 alpha prolong survival in neutropenic mice with a lethal C. albicans infection.