Lymphotoxin-beta and TNF regulation in T cell subsets: Differential effects of PGE(2)

The effects of prostaglandin E(2) (PGE(2)) On lymphotoxin beta (LT-beta) and tumour necrosis factor alpha (TNF) were assessed in murine CD4(+) Th-1 and Th-2 T cell clones, LT-beta mRNA was constitutively expressed by both T cell subsets, However, PGE(2) inhibited its accumulation only in Th-1, but not Th-2 clones, PGE(2) inhibited TNF mRNA accumulation and production and release of bioactive material by both Th-1 and Th-2 T cells, The effects of PGE(2) were also evaluated on production of IL-3, another cytokine produced by both T cell subsets, and interleukin 4 (IL-4), which is produced only by Th-2 cells, Though IL-3 was produced by both T cell subsets it was only inhibited in Th-1 cells, a pattern similar to that observed for LT-beta, Accumulation of IL-3 mRNA in Th-2 cells was not inhibited by PGE(2), These results demonstrate that PGE(2) does not affect LT-beta, IL-4, or IL-3 in Th-2 cells, but inhibits TNF mRNA accumulation and production in this T cell subset, Thus, TNF appears to be the only cytokine susceptible to inhibition by PGE(2) in Th-2 cells, The fact that PGE(2) inhibits LT-beta and IL-3 in Th-1 but not Th-2 cells points to a different mechanism of regulation of the same cytokine in different subsets, The mechanisms that contribute to TNF mRNA accumulation also may differ in the two CD4(+) T cell subsets, because cycloheximide superinduced TNF mRNA in Th-2 cells, but not in Th-1 cells, The inhibitory effects of PGE(2) on TNF mRNA accumulation by either T cell subset did not require de novo protein synthesis since preincubation with the protein synthesis inhibitor, cycloheximide, did not alter the PGE(2)-mediated effects, Cross-regulation of cytokine production and function has been demonstrated for both T cell subsets, and PGE(2) may modulate the outcome of an immune response via differential regulation of cytokine production. (C) 1997 Academic Press Limited.