NEUROLOGICAL AND PSYCHIATRIC ADVERSE-EFFECTS OF IMMUNOLOGICAL THERAPY

Immunological therapy with cytokines can cause acute, subacute, delayed and, occasionally, irreversible toxicity to the CNS. Neurotoxic adverse effects are manifested by changes in cognitive, motor and emotional functioning. Although these changes are sometimes global in nature, most subacute neurotoxic symptoms attributable to interferon-a, interleukin-2 and tumour necrosis factor are specific to frontal-subcortical dysfunction and involve specific neuroanatomical and neurochemical systems. The symptoms observed typically include memory deficits, difficulties with motivation and flexible thinking (frontal lobe executive function) and motor coordination. Reasoning, language functions and visual perception are generally not affected. Depression and other psychiatric presentations are common and appear to be due to the biochemical changes induced by cytokines rather than psychological reactions to the illness for which the agents are administered. The mechanism of action of cytokines on brain function may include alterations in neurotransmitter function (mostly involving opioid and dopaminergic systems), induction of the release of neuroendocrine hormones and of other cytokines. Improved understanding of the mechanism of cytokine action in the brain is guiding the development of treatment interventions to reduce or eliminate CNS toxicity without sacrificing therapeutic efficacy. In addition, studies of cytokine neurotoxicity have advanced our knowledge of the normal role of these agents in the CNS.