ABSTRACT
Cytokines are polypeptide mediators with diverse and often overlapping biological activities. Released by all nucleated cells, cytokines provide a mechanism for intercellular communication that is not dependent on cell contact. Cytokines rarely function in isolation but participate in cascades or networks of cytokines released in response to an infectious challenge. This cascade of cytokine release results in variable concentrations of different cytokines at variable times within a particular tissue. The resultant cytokine milieu in the tissue regulates all aspects of the host response to infection. In the early innate immune response to infection, cytokines activate resident cells to phagocytize an infectious pathogen and regulate recruitment of additional inflammatory cells from the vasculature. During the evolution of the adaptive immune response, cytokines influence the type of lymphocyte response generated both locally and in regional lymphoid tissue. Cytokines also circulate to the bone marrow to stimulate a leukocyte response to infection. During infection, most of the activity of cytokines takes place within the infected tissue. However, with extensive infection or as a result of pathogen virulence factors, cytokines may be released from the tissue compartment and exert toxic effects on the host. Clinically, these systemic effects of cytokines may be manifest as
sepsis, shock, or the adult respiratory distress syndrome. Thus, cytokines are involved in every aspect of host defense against infection and play a determining role in whether an infection is cleared or results in death of the host.
