Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-α treatment. While IFN-α is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-α in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-α on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-α or placebo using a double-blind, placebo-controlled crossover design. IFN-α resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-α acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-α on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-α.
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