Biology Reference
In-Depth Information
14
Multiple Roles of Cytokines in HIV
Infection, Replication, and Therapy
Massimo Alfano and Guido Poli
AIDS Immunopathogenesis Unit, San Ra¨aele Scienti®c Institute, Milano, Italy
THE CYTOKINE NETWORK
Cytokines are soluble molecules produced by both immune and nonimmune
cells such as endothelial and epithelial cells. When the ®rst biological activities,
later de®ned as ``lymphokines'' and ``monokines,'' were discovered, the general
assumption was that each molecule was endowed with a unique biological
function. In contrast, it is now well recognized that cytokines are characterized
by pleiotropy (one molecule, multiple targets) and redundancy (di¨erent cyto-
kines exert similar biological e¨ect on the same cell) ( Paul, 1989; Paul and
Seder, 1994). In addition, cytokines have usually more than one receptor (che-
motactic cytokines, or chemokines, in this regard, are extremely promiscuous),
whereas individual cells express multiple receptors for di¨erent cytokines, thus
allowing complex synergistic or antagonistic interactions.
Cytokines control both innate and speci®c immune responses, the entire
process of in¯ammation, and its turning-o¨; they can also exert mitogenic activ-
ities or induce growth arrest, cell di¨erentiation, and death by regulating com-
plex apoptotic pathways ( Dinarello, 1998). Unlike hormones, they are usually
characterized by short-term and self-limited action (autacoids) ( Paul, 1989).
In this regard, cytokines mediate their e¨ects via high-a½nity binding to cell
surface receptors, and they can in¯uence cells surrounding the site of produc-
tion in a paracrine and autocrine fashion.
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