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Sensitivity Difference to the Suppressive Effect of Prostaglandin E₂ Among Mouse Strains: A Possible Mechanism to Polarize Th2 Type Response in BALB/c Mice

Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan

PGE₂ has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE₂ in IFN- production by Staphylococcus aureus Cowan I-stimulated spleen cells from several mouse strains such 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- production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE₂ production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE₂ were exogeneously added to spleen cells, PGE₂ showed a stronger suppressive effect on IFN- production in spleen cells from BALB/c mice than from other strains of mice. This suppressive effect of PGE₂ in BALB/c mice mainly depended on IL-12p70 production by APCs. More PGE₂ binding sites were found in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE₂ was due to the difference of the number of PGE₂ receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN- 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 PGE₂ is important for Th1 activation via IFN- and IL-12p70 production in vitro and in vivo and that PGE₂ is one of the pivotal factors in the Th2-dominant immune response in BALB/c mice.

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