The relationship between cytokines and pain/depression: a review and current status

Cytokines are small protein molecules secreted in response to immune stimuli. Recent research has outlined important roles for proinflammatory cytokines in the cascade of normal physiologic responses to environmental stresses, encompassing so-called sickness behavior that is thought to be an adaptive response to infection and other illnesses. Cytokines are involved in signaling that activates central nervous system glial cells. This activation is part of a poorly understood interaction between immune challenge or injury and host that can lead to the development or facilitation of persistent mood symptoms or pathologic pain. This article reviews evidence that may enhance our understanding of how pathologic symptoms, such as mood disorders and neuropathic pain, may emerge from proinflammatory cytokine activation. Possible conceptualizations of these illnesses and potential treatment implications are explored.