Proinflammatory cytokines and treatment of disease

Bacterial infections in the immunocompromised host cause considerable mortality, and even recently developed antimicrobial strategies often fail to cure these infections, especially in granulocytopenic patients. Cytokines and hematopoietic growth factors have been shown to stimulate host defense mechanisms in vitro and in vivo. The possible role of the proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor-alpha, IL-6, and IL-8 as modulators of host resistance to bacterial infections is discussed. Interleukin-1 has been effective in various animal models of potentially lethal bacterial infection, even during severe granulocytopenia. The protective mechanism of IL-1 may be mediated by downregulation of cytokine receptors and cytokine production and induction of acute phase proteins. Moreover, in subacute and chronic infections IL-1 interferes with microbial outgrowth via mechanisms that have only been partly elucidated.