Background: Like major depression, dysthymia has been associated with elevated production of interleukin-1 (IL-1β) in mitogen-stimulated lymphocytes. In the present investigation, we assessed whether the elevated IL-1β production in dysthymic patients would normalize following treatment with sertraline.Methods: The production of IL-1β was determined in dysthymic patients and in nondepressed control subjects. Patients then received 12 weeks of doses of either sertraline or placebo in a double-blind trial, after which cytokine production was again determined.Results: Basal IL-1β was elevated in dysthymic patients relative to control subjects. Cytokine production was modestly correlated with the severity of symptoms and with the age of illness onset. Relative to placebo treatment, sertraline attenuated the symptoms of depression; however, this was not accompanied by normalization of IL-1β production.Conclusions: While dysthymia is associated with elevated IL-1β production, the failure for the cytokine to normalize following symptom alleviation suggests that either the IL-1β may be a trait marker of the illness, or that more sustained treatment is necessary to reduce cytokine production. Given the neuroendocrine and central neurochemical consequences of exogenously administered IL-1β, the possibility ought to be explored that increased IL-1β production may play a role in the pathophysiology of dysthymia. Copyright (C) 1999 Society of Biological Psychiatry.