Options for the treatment of serious infections with interleukin-1

In this paper, the effects of recombinant human interleukin-1 (IL-1) on non-specific resistance to infection are reviewed. In experiments in neutropenic mice, a single injection of a low dose of IL-1 (8-800 ng) appears to protect against death from lethal Pseudomonas aeruginosa and Candida albicans infections. In non-neutropenic mice protection can also be obtained with such dosages of IL-1 in infection caused by Klebsiella pneumoniae or Listeria monocytogenes. Low dosages of IL-1 are also able to prevent lethal cerebral malaria in mice. No effect has been found in murine cytomegalovirus infection. With the exception of C. albicans infection and malaria, protection is only obtained if IL-1 is given before the infection. The mechanism of protection has not been elucidated; in the Pseudomonas and Klebsiella infection, it could be demonstrated that survival was not due to a direct antibacterial effect of IL-1, not due to the action of granulocytes or increased hematopoietic recovery and not due to activation of macrophages and increased bactericidal mechanisms. In the experimental Listeria infection however, animals treated with IL-1 had lower bacterial counts in their organs. Since the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) are much less potent than IL-1 in these protection experiments, it is very unlikely that they are endogenous mediators of the protection induced by IL-1. The effect is not mediated via the cyclooxygenase pathway, since premedication with ibuprofen does not influence the protective effect of IL-1. Taking these data together, it is felt that IL-1 holds promise as a therapeutic agent in humans.