INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST PREVENTS STAPHYLOCOCCUS-EPIDERMIDIS-INDUCED HYPOTENSION AND REDUCES CIRCULATING LEVELS OF TUMOR-NECROSIS-FACTOR AND IL-1-BETA IN RABBITS
K. Aiura et al., INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST PREVENTS STAPHYLOCOCCUS-EPIDERMIDIS-INDUCED HYPOTENSION AND REDUCES CIRCULATING LEVELS OF TUMOR-NECROSIS-FACTOR AND IL-1-BETA IN RABBITS, Infection and immunity, 61(8), 1993, pp. 3342-3350
Similar to shock in gram-negative sepsis, shock from gram-positive org
anisms is mediated, in part, by tumor necrosis factor (TNF) and interl
eukin-I (IL-1). In the present study, rabbits were infused with IL-1 r
eceptor antagonist (IL-1ra) prior to and during Staphylococcus epiderm
idis-induced hypotension. After injection of bacteria, a maximal fall
in mean arterial pressure to -42% below baseline occurred at 200 min i
n vehicle-treated animals compared with a nonsignificant decrease of o
nly 7% in the IL-1ra-treated group (P < 0.01, vehicle versus IL-1ra).
A similar attenuation was observed in the fall in systemic vascular re
sistance (P < 0.05). After the injection of S. epidermidis, TNF levels
rose to a peak elevation of 475 +/- 160 U/ml in vehicle-treated rabbi
ts, but in rabbits receiving IL-1ra, maximal TNF levels rose only to 8
5 +/- 23 U/ml (P < 0.01). Plasma IL-1beta reached maximal concentratio
ns at 180 min of 364 +/- 71 pg/ml in vehicle-treated animals but only
145 +/- 12 pg/ml in rabbits given IL-1ra (P < 0.05). The reductions in
TNF and IL-1 were not due to interference by IL-1ra in the respective
assays. In vitro, IL-1ra inhibited S. epidermidis-induced TNF from mo
nonuclear cells by 31% +/- 11%, from spleen cells by 17% +/- 4% (P < 0
.05), and from whole blood by 42% +/- 17%. Despite the near reversal o
f the fall in mean arterial pressure and systemic vascular resistance
in IL-1ra-treated rabbits, leukopenia and thrombocytopenia were unaffe
cted. These results demonstrate that IL-1ra blocks shock-like hemodyna
mic parameters and reduces circulating IL-1 and TNF levels in a model
of gram-positive sepsis.