Interferons, serotonin and neurotoxicity.
BACKGROUND
Interferons are a class of cytokines profoundly affecting immune function. Several interferons are now synthesized and used clinically, notably for viral diseases and cancer. In addition to their desired immune effects, interferons cause a number of toxicities, including prominent effects on the nervous system.


METHODS
This literature review focused on the incidence of depression associated with interferon treatment. Possible neurochemical mechanisms and remedial strategies were also considered.


RESULTS
Interferon treatment, particularly with the alpha subtype, is unquestionably linked with depression, but the strength of association is uncertain because of erratic ascertainment and pretreatment co-morbidity. A likely pathogenic mechanism has been described, involving interferon suppression of serotonin synthesis. Controlled treatment trials of interferon-induced depression are not yet available.


CONCLUSIONS
Neurotoxicity substantially limits the use of interferons. At least some of the risk of depression appears to derive from their anti-serotonergic effects, consistent with the large body of evidence pointing to a general link between serotonin and affective illness. Vigilant detection and aggressive treatment of depression is necessary to optimize interferon treatment of many patients.
Menkes
D B
DB
Dunedin School of Medicine, University of Otago and Dunedin Hospital, New Zealand.
MacDonald
J A
JA
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003866:Depressive Disorder / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D007372:Interferons / Q000009:adverse effects* / Q000627:therapeutic use; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors; D012701:Serotonin / Q000502:physiology*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D012701:Serotonin; D007372:Interferons