What can we learn from fish? An evolutionary perspective of pro-inflammatory cytokines

All jawed vertebrates (Gnathostomes) possess a complex immune system, which is capable of adaptive (anticipatory) and innate (natural) immune responses(1,2). In contrast, jawless vertebrates (Agnathes) and invertebrates lack an adaptive immune response and its defence depends exclusively on the innate immunity (Fig. 1). The coordination of adaptive and innate immune responses is largely mediated by cytokines(3). This pivotal role of cytokines raises the question of whether or not these molecules have been highly conserved through evolution. In fact, earlier studies described the biological activities of several cytokines in primitive vertebrates and even invertebrates(4). However, without knowing the amino acid or gene sequences of putative non-mammalian cytokine analogues, it is not possible to demonstrate unequivocally a phylogenetic relationship between mammalian cytokines and their invertebrate and primitive vertebrate functional analogues. Recently, cytokines which have been well characterised within mammals have begun to be cloned and sequenced within non-mammalian vertebrates, including amphibians, birds, bony fish, cartilaginous fish and jawless fish(5,6).