The enigma of cytokine redundancy

SUMMARY The redundancy of many cytokine functions that was first noted in vitro has now been confirmed in vivo with the demonstration that some of these functions can occur in mice rendered deficient in a cytokine or cytokine receptor by gene inactivation. Other functions are ablated in these mice, suggesting that they are cytokine‐specific. Although some of the underlying mechanisms have been identified, it remains unclear why certain activities of a cytokine should be unique and others redundant. It is proposed that compensatory mechanisms exist only for those cytokine functions whose inappropriate or excessive activation would not be pathogenic or whose importance justifies this risk. Conversely, cytokine‐specific functions might be those that should be tightly regulated to avoid the pathological consequences of their inadvertent expression.