By. Kang et al., Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4(+) T cells, BR J PHARM, 130(3), 2000, pp. 581-586
1 Interleukin-12 (IL-12) plays a central role in the immune system by drivi
ng the immune response towards T helper 1 (Th1) type responses characterize
d by high IFN-gamma and low IL-4 production. In this study we investigated
whether retinoid-mediated inhibition of interleukin-12 production in mouse
macrophages could regulate cytokine profile of antigen (Ag)-primed CD4(+) T
h cells.
2 Pretreatment with retinoids (9-cis-RA, all-trans-RA, TTNPB) significantly
inhibited IL-12 production by mouse macrophages stimulated with lipopolysa
ccharide (LPS) or heated-killed Listeria monocytogenes (HKL). Retinoid-pret
reated macrophages reduced their ability to induce IFN-gamma and increased
the ability to induce IL-4 in Ag-primed CD4(+) T cells.
3 Addition of recombinant IL-12 to cultures of retinoid-pretreated macropha
ges and CD4(+) T cells restored IFN-gamma production in CD4(+) T cells.
4 The in vivo administration of 9-cis-RA resulted in the inhibition of IL-1
2 production by macrophages stimulated in vitro with either LPS or HKL, lea
ding to the inhibition of Th1 cytokine profile (decreased IFN-gamma and inc
reased IL-4 production) in CD4(+) T cells.
5 These findings may explain some known effects of retinoids including the
inhibition of encephalitogenicity, and point to a possible therapeutic use
of retinoids in the Th1-mediated immune diseases such as autoimmune disease
s.