Targets for modulating cytokine responses in inflammatory and infectious diseases

Abstract

Cytokines were discovered in the 1950s by workers studying fever and by those interested in cellular anti-viral defences and in the 1960s by immunologists interested in monocyte-lymphocyte interactions. Further discoveries and rediscoveries were made in the 1970s and 1980s and the term cytokine (first introduced by Cohen in the 1970s) now describes a very large number of proteins and glycoproteins. These proteins are part of the cell-to-cell signalling requirements of the multicellular organism in order to maintain homeostasis. The importance of cytokines is increasingly being delineated by the development of animals in which one or more selected cytokine genes have been disrupted (knocked out) by homologous recombination. Many of these knockout animals show increased sensitivity to infectious microorganisms. Others, such as those where interleukin-2 (IL-2) or interleukin-10 (IL-10) genes have been knocked out, reveal severe local inflammatory responses which appear to be due to aberrant responses to the animal’s commensal micro-flora.