Cytokines and chemokines in Mycobacterium tuberculosis infection

Cytokines are soluble, small proteins that are produced by cells and act in a largely paracrine manner to influence the activity of other cells. Currently, the term "cytokine" describes proteins such as the tumor necrosis factor family, the interleukins, and the chemokines. Virtually every nucleated cell can produce and respond to cytokines, placing these molecules at the center of most of the body's homeostatic mechanisms (1). Much of our knowledge of the function of cytokines has been derived from studies wherein homeostasis has been disrupted by infection and the absence of specific cytokines results in a failure to control the disease process. In this context, infection with Mycobacterium tuberculosis has proven to be very informative and has highlighted the role of cytokines in controlling infection without promoting uncontrolled and damaging inflammatory responses (2 - 4). Herein, we focus on the key cytokine and chemokines that have been studied in the context of human TB using experimental medicine as well as M. tuberculosis infection of various animal models, including non-human primates (NHPs), mice, and rabbits. Perhaps the most important message of this review is that in a complex disease such as TB the role of any one cytokine cannot be designated either "good" or "bad" but rather that cytokines can elicit both protective and pathologic consequences depending on context.