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Interleukin 12
Vellalore N. Kakkanaiah, Ph.D.
Interleukin-12, originally known as the natural killer cell stimulatory factor, is a multifunctional cytokine produced by monocytes/macrophages, B cells, and other accessory cells in response to bacteria, bacterial products, or parasites.1 IL-12 induces IFN-g secretion by T and NK cells, acts as a growth factor for activated T and NK cells, enhances the lytic activity of NK/lymphokine-activated killer (NK/LAK) cells, and facilitates specific cytotoxic T-cell (CTL) responses.2,3 IL-12 plays an important role in stimulating the differentiation of T-helper type 1 (Th1) responses from naive Th cells by acting as a co-stimulus required for maximum IFN-g secretion by antigen-activated Th1 cells.4 IL-12 indirectly stimulates B-cell growth and switching of IgG alloantibody subclass through the production of IFN-g.5,6 IL-12 induces effective anti-tumor immunity along with other co-stimuli such as IL-2 or B7.1 of HIV.7,8 IL-12 production is decreased in cells from HIV-positive individuals.9 In cultures, gp120 of HIV is an inducer of IL-12 expression in monocytes/macrophages and is dependent on IFN-g.10 IL-12 is capable of indirectly down-regulating HIV proliferation in macrophage cultures reconstituted with autologous PBMC and of directly suppressing HIV replication in purified macrophage cultures.11 IL-12 restores IFN-g production and cytotoxic responses in visceral leishmaniasis,12 and inhibits endotoxin-induced inflammation in the eye.13
REFERENCES
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- Murphy EE, Terres G, Macatonia SE, et al. B7 and interleukin 12 cooperates for proliferation and interferon-g production by mouse T helper clones that are unresponsive to B7 costimulation. J Exp Med 1994;180:223-31.
- Li L, Young D, Wolf SF, Choi YS. Interleukin-12 stimulates B cell growth by inducing IFN-g. Cell Immunol 1996;168:133-40.
- Gracie JA, Bradley JA. Interleukin-12 induces interferon-g-dependent switching of IgG alloantibody subclass. Eur J Immunol 1996;26:1217-21.
- Wigginton JM, Kuhns DB, Back TC, Brunda MJ, Wiltrout RH, Cox GW. Interleukin 12 primes macrophages for nitric oxide production in vivo and restores depressed nitric oxide production by macrophages from tumor-bearing mice: implications for the antitumor activity of interleukin 12 and/or interleukin 2. Cancer Res 1996;56:1131-6.
- Zitvogel L, Robbins PD, Storkus WJ, et al. Interleukin-12 and B7.1 co-stimulation cooperate in the production of effective antitumor immunity and therapy of established tumors. Eur J Immunol 1996;26:1335-41.
- Chougnet C, Wynn TA, Clerici M, et al. Molecular analysis of decreased interleukin-12 production in persons infected with human immunodeficiency virus. J Infec Dis 1996;176:46-53.
- Fantuzzi L, Gessani S, Borghi P, et al. Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: requirement of gamma interferon for IL-12 secretion. J Virol 1996;70:4121-4.
- Akridge R, Reed SG. Interleukin-12 decreases human immunodeficiency virus type 1 replication in human macrophage cultures reconstituted with autologous peripheral blood mononuclear cells. J Infect Dis 1996;173:559-64.
- Bacellar O, Brodskyn C, Guerreiro J, et al. Interleukin-12 restores interferon-g production and cytotoxic responses in visceral leishmaniasis. J Infect Dis 1996;173:1515-8.
- Whitcup SM, Rizzo LV, Lai JC, Hayashi S, Gazzinelli R, Chan C-C. IL-12 inhibits endotoxin-induced inflammation in the eye. Eur J Immunol 1996;26:995-9.
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