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CUTTING EDGE |
Production In Vivo1
*
Department of Internal Medicine, Division of Hematology/Oncology, and
Department of Molecular Virology, Immunology, and Medical Genetics, Division of Human Cancer Genetics, and the Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210
Sequential administration of LPS to SCID mice results in the
generalized Shwartzman reaction, manifesting as rapid mortality via
cytokine-induced shock. Here we demonstrate that in vivo neutralization
of IL-15 before LPS priming significantly reduced lethality in this
reaction (p = 0.0172). We hypothesize that LPS
priming induces IL-12 and IL-15 that costimulate NK cell-derived
IFN-
. Such IFN- may then in turn sensitize macrophages to elicit
the Shwartzman reaction following a subsequent LPS challenge.
Supporting this, IL-12 and IL-15 synergized to induce murine NK cell
IFN- production in vitro. LPS stimulation of SCID mouse splenocytes
resulted in measurable IFN- production, which was reduced when IL-15
was neutralized or IL-2/15Rß was blocked. Pretreatment with either
anti-IL-2/15Rß or anti-IL-15 Abs reduced serum IFN-
protein following LPS administration to SCID mice. Collectively, these
data provide the first in vivo evidence that IL-15 participates in
LPS-induced innate immune IFN- production and significantly
contributes to the lethal Shwartzman reaction.
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