Design
Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E₂ (PGE₂).

Results
Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P<.05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE₂ resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane-associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H-8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury.

Conclusions
These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE₂, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation.

(Arch Surg. 1994;129:1284-1289)