Cytokine therapies including interferon-alpha (IF-alpha) and interleukin-2 (IL-2) have been used for cancers and chronic diseases including melanoma, hepatitis C, and multiple sclerosis. However, they may cause neuropsychiatric side effects (Myint et al., 2009).

These side effects include depression, anxiety, psychosis, hypomanic mood, and cognitive dysfunctions. Some patients may continue to have cognitive problems even after stopping taking the drugs (Myint et al., 2009).

Animal studies have confirmed that the cytokine therapies may result in anxiety, depressive-like, and sickness behaviors, as well as social anhedonia with higher levels of pro-inflammatory cytokines (Myint et al., 2009).

Studies have found that the pro-inflammatory cytokines may stimulate some enzymes such as indoleamine 2-3, dioxygenase (IDO) (Myint et al., 2009). Such changes may promote the tryptophan degradation into kynurenine with lower levels of tryptophan in the brain. As a result, lower levels of the neurotransmitter serotonin may be produced that cannot maintain the normal mood conditions.

The imbalance in the catabolic kynurenine pathway and neurotransmitter-associated networks are critical for abnormal psychophysiological functions (Myint et al., 2009). Such imbalance may be caused by cytokine therapies and result in psychiatric disorders such as anxiety and depression. More studies are needed to find out the possibilities of maintaining the immune balance while using cytokine therapies.

Myint AM, Schwarz MJ, Steinbusch HW, Leonard BE. Neuropsychiatric disorders related to interferon and interleukins treatment. Metab Brain Dis. 2009 Mar;24(1):55-68. doi: 10.1007/s11011-008-9114-5.

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