Evolution of the interleukins.

As the adaptive immune system arose in jawed vertebrates, a reasonable working hypothesis is that cytokines involved exclusively in controlling the adaptive immune system, e.g. T1 and T2 cytokines, will only be found in jawed vertebrates whilst those with a role in innate responses, e.g. type I IFNs or pro-inflammatory cytokines, will be universal, or have functional equivalents in 'lower' animals. Progress to date in cloning cytokines, including interleukins, in vertebrates outside of mammals is limited and non-existent in invertebrates. T1 and T2 interleukins have only been cloned in birds. Receptors for T1 and T2 interleukins have been cloned in fish, however, suggesting the presence of the corresponding interleukins. Pro-inflammatory interleukins have been cloned in birds, fish and amphibia, but not reptiles. Cross-reactive bioassays, polyclonal antisera and mAbs suggest that an IL-6-like factor exists in starfish, as yet the only evidence for innate immune response cytokines in 'lower' animals.