Interleukin-12 (IL12) is a disulfide linked heterodimeric cytokine ori
ginally identified as a product of EBV-transformed B cell lines; monoc
ytes/macrophages are the physiologically most relevant producers of IL
12 in response to bacterias or intracellular parasites. Although IL12
has an enhancing effect on the survival and growth of hematopoietic pr
ogenitor cells, most of the IL12 biological activity has been describe
d on T and NK cells, on which it induces production of lymphokines, pr
imarily IFN gamma, enhances cytotoxic activity and, in cooperation wit
h other stimuli, increase proliferation. Early during infection, IL12
acts as a proinflammatory cytokine by inducing IFN gamma production fr
om NK and T cells which in turn activates phagocytic cells. IL12 then
sets the stage for the ensuring adaptive immune response by stimulatin
g generation of T helper type 1 (Th-1) cells and by activating cell-me
diated resistance mechanisms against several pathogens. Several studie
s have now established the IL-12 plays an early and major role in the
resistance to bacterial and parasitic infections by activating macroph
ages through induction of IFN gamma from NK and T cells. Thus, because
of its ability to induce Th-1 responses and efficient cell-mediated i
mmunity, IL12 has several potential therapeutic uses in infectious dis
eases and in cancer patients. Natural IL12 appears to provide a regula
tory link between innate resistance and the development of the antigen
-specific adaptive immune response. The recombinant protein also has t
herapeutic potential because of its activity against tumors and infect
ions, and its effectiveness as an adjuvant enhancing cell-mediated imm
unity in vaccination.