Nl. Brown et al., The regulation of prostaglandin output from term intact fetal membranes byanti-inflammatory cytokines, IMMUNOLOGY, 99(1), 2000, pp. 124-133
Prostaglandins are some of the main mediators which control parturition, an
d their production by intrauterine tissues can be up-regulated by pro-infla
mmatory cytokines. Anti-inflammatory cytokines may oppose these effects, an
d in this study we have investigated how two such cytokines affected fetal
membrane function. Interleukin-10 (IL-10) inhibited the output of prostagla
ndin E-2 (PGE(2)) from intact fetal membranes under basal and lipopolysacch
aride (LPS)-stimulated conditions, and there was a parallel decrease in the
expression of mRNA for COX-2. IL-10 also inhibited the production of inter
leukin-1 beta (IL-1 beta) and the expression of mRNA for IL-1 beta, indicat
ing that this cytokine has a broad anti-inflammatory effect. Transforming g
rowth factor-beta 1 (TGF-beta 1), which is generally considered to be anti-
inflammatory had opposite effects on PGE(2) production, in that it increase
d the output of PGE(2) for up to 8 hr. TGF-beta 1 increased levels of type-
2 cyclooxygenase (COX-2) and cytosolic phospholipase A(2) (cPLA2) protein,
and also activated the cPLA2 enzyme present; the profile of effects is simi
lar to that of the pro-inflammatory cytokine IL-1 beta, and was not expecte
d. Combinations of TGF-beta 1 with IL-1 beta also increased PGE2 output and
caused appropriate changes in prostaglandin pathway enzymes, whereas TGF-b
eta 1 and IL-1 alpha had more limited effects. Further studies are needed t
o establish the physiological significance of these findings, but TGF-beta
1 does not seem to act as an inhibitory cytokine in intact fetal membranes
at: term.