NEUROLOGICAL AND PSYCHIATRIC ADVERSE-EFFECTS OF IMMUNOLOGICAL THERAPY

Immunological therapy with cytokines can cause acute, subacute, delaye d and, occasionally, irreversible toxicity to the CNS. Neurotoxic adve rse effects are manifested by changes in cognitive, motor and emotiona l functioning. Although these changes are sometimes global in nature, most subacute neurotoxic symptoms attributable to interferon-a, interl eukin-2 and tumour necrosis factor are specific to frontal-subcortical dysfunction and involve specific neuroanatomical and neurochemical sy stems. The symptoms observed typically include memory deficits, diffic ulties with motivation and flexible thinking (frontal lobe executive f unction) and motor coordination. Reasoning, language functions and vis ual perception are generally not affected. Depression and other psychi atric presentations are common and appear to be due to the biochemical changes induced by cytokines rather than psychological reactions to t he illness for which the agents are administered. The mechanism of act ion of cytokines on brain function may include alterations in neurotra nsmitter function (mostly involving opioid and dopaminergic systems), induction of the release of neuroendocrine hormones and of other cytok ines. Improved understanding of the mechanism of cytokine action in th e brain is guiding the development of treatment interventions to reduc e or eliminate CNS toxicity without sacrificing therapeutic efficacy. In addition, studies of cytokine neurotoxicity have advanced our knowl edge of the normal role of these agents in the CNS.