Suppression of interleukin 2 production in an animal model of thermal injury is related to prostaglandin synthesis
J. J. Wood, J. T. Grbic, M. L. Rodrick, A. Jordan and J. A. Mannick
We performed studies using an animal model of thermal injury to confirm the
observed decrease in interleukin 2 (IL-2) production in burned patients and
to explore the underlying mechanisms. Ten mice subjected to a 25% scald
were compared with ten anesthetized littermates (controls) and six
untreated mice (normal mice) 1, 3, 5, 7, 10, 14, and 21 days after burn.
Production of IL-2 by splenocytes was stimulated by concanavalin A alone,
or in the presence of the cyclooxygenase inhibitor indomethacin or
flurbiprofen. The IL-2 content of the resulting supernatant was determined
by the response of the IL-2-dependent cell line CTLL-2. The IL-2 production
was significantly suppressed in the burned mice at three days (mean +/-
SEM, 30.9% +/- 5.2%), five days (19% +/- 5.5%), seven days (41.6% +/-
6.4%), and 21 days (20% +/- 4.5%). Significant enhancement of IL-2
production by indomethacin was seen in the burned group (mean, 95%), but
not in controls (mean, 23.8%) or normal mice (mean, 17.2%), and similar
effects were seen with flurbiprofen. In separate experiments the effects of
exogenous prostaglandin E2 on lymphocyte blastogenesis and IL-2 production
were studied, and an increased susceptibility to the inhibitory effects of
prostaglandin E2 was observed following thermal injury.
