Interferon-ɑ and sickness behaviour : a study of the dose and time dependency of interferon-ɑ-induced anhedonia and fever

Abstract

The use of recombinant human Interferon-ɑ2A for the treatment of more than 14 malignancies and virologic diseases is acknowledged world-wide, in over 40 countries. However, its use has been hampered by the many side effects accompanying its therapy, of which depression and suicidal ideations are the extreme cases. Significant research effort has gone into understanding the neural and molecular mechanisms of action of this cytokine, but to date there exist gaps in our understanding of the underlying fine mechanistic details. The side effects of Interferon-a can be described as typical Sickness Behaviour (a coordinated set of behavioural changes that develop in sick individuals during the course of an infection). A Model of Anhedonia was used as the paradigm within which to test and investigate the dose and time dependency of the effects of recombinant human Interferon-a2A (rHIFN-ɑ2A)· The species-specificity of rHIFN-ɑ2A in rats was also studied within this paradigm. The effects of IFN on temperature were used to monitor the activity of the drug in the rats, while anhedonia (measured as a change in the consumption and preference for 1%, 8% and 32% sucrose solutions) was used to assess the impact of IFN on positive reinforcement. From the results obtained rHIFN-ɑ2A was confirmed to be 100 to 1000 times less potent than rat interferon-ɑA (RIFN-ɑA) in rats. More importantly, new insights into the mechanisms of action of rHIFN-ɑ2A on anhedonia and fever were suggested. However, the whole picture is far from complete and this project just represents a first attempt to improve our knowledge of Interferon neurochemistry. This and future studies could eventually lead to the development of appropriate drugs that dampen the undesirable side effects of Interferon-ɑ therapy, allowing patients to make full use of an otherwise effective therapy.