Interleukin-12 and infectious diseases: a potential novel therapy

Interleukin-12 (IL-12) is emerging as a central component of both innate and acquired immunity. The multiplicity of biological activities associated with this cytokine, particularly the stimulation of cell-mediated immunity, suggests that it may be crucial in the control of extracellular and intracellular infections. In in vitro studies, IL-12 production is initiated rapidly after infection with a variety of viral, parasitic, fungal and bacterial agents. This induction correlates well with the reported resistance or susceptibility of animals to infection with these agents. Other factors may, however, influence responses in vivo, including host genetic make-up, microbial load and the induction of antagonistic cytokine pathways, notably IL-4 and IL-10. In some situations, IL-12 may direct immune responses to inappropriate pathways, and worsen disease, so that careful consideration of the type of required immune response is needed before IL-12 therapy is initiated. IL-12 treatment may also be useful in promoting protective immune responses to vaccines, allowing systemic immunisation with lower doses, or even normally non-immunogenic preparations, of antigen. Finally, IL-12 has been demonstrated to act in concert with standard antimicrobial chemotherapy in viral, parasitic, fungal and bacterial infections, allowing a reduction in the dose of the agent used and providing hope that such combination therapy may more effectively control drug-resistant strains of infectious agents.