Sensitivity difference to the suppressive effect of prostaglandin E2 amongmouse strains: A possible mechanism to polarize Th2 type response in BALB/c mice

PGE, has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE, in IFN-gamma production by Staphylo coccus aureus Cowan I-stimulated spleen cells from several mouse strains su ch as BALB/c, C3H/HeN, and C57BL/6, When spleen cells were pretreated with indomethacin (cyclooxygenase (COX)-1 and COX-2 inhibitor) or NS-398 (COX-2- specific inhibitor), S. aureus Cowan I -induced IFN-gamma production was in creased more markedly in spleen cells from BALB/c mice than from C3H/HeN an d C57BL/6 mouse. However, PGE(2) production was not significantly different among spleen cells from three mouse strains. When various concentrations o f PGE(2) were exogeneously added to spleen cells, PGE(2) showed a stronger suppressive effect on IFN-gamma production in spleen cells from BALB/c mice than From other strains of mice. This suppressive effect of PGE(2) in BALB /c mice mainly depended on IL-12p70 production by APCs, More PGE(2) binding sites were Pound in BALB/c spleen cells than in C3H/HeN spleen cells, indi cating that the sensitivity difference to the suppressive effect of PGE(2) was due to the difference of the number of PGE(2) receptors. The administra tion of NS-398 into BALB/c mice enhanced Ag-specific IFN-gamma production, but not IL-4 production. This effect is the same as IL-12 administration in vivo. From these results, we propose that the modulation of PGE(2) is impo rtant for Th1 activation via IFN-gamma and IL-12p70 production in vitro and in vivo and that PGE(2) is one of the pivot al factors in the Th2-dominant immune response in BALB/c mice.