LPS-inducible responses in severe combined immunodeficiency (SCID) mice

Abstract

Lipopolysaccharide (LPS) is a potent bacterial product that has been shown to act on many different cell types both in vivo and in vitro. Injection of immunologically competent mice with LPS results in increased serum cytokine levels, followed by an array of pathophysiologic alterations that can ultimately lead to death. In this study, we examined the response of severe combined immunodeficient (SCID) mice to LPS. These mice lack mature T and B cells and have been shown to be an important model for analyzing the contribution of innate immune responses to infectious agents. Injection of SCID mice with LPS resulted in increases in CSF, TNF, and IFN levels in serum that were similar to the responses of immunocompetent controls. In response to LPS, both SCID and control mice exhibited similar levels of hypoglycemia. LPS-induced toxicity was assessed in D(+)-galactosamine-sensitized animals. SCID mice were comparably sensitive to the lethal effects of LPS as control BALB/c mice. To assess the role of natural killer (NK) cells in LPS-induced cytokine responses, BALB/c and SCID mice were injected with anti-asialo-GM1 antibody prior to injection of LPS. No significant effect on LPS-induced CSF or blood glucose levels were seen, although NK-depleted SCID mice produced somewhat more IFN in response to LPS than normal mice. Thus, NK cells are not a major source of these early LPS-induced cytokines. These data suggest that mature T and B cells and NK cells do not contribute to the initial wave of cytokines produced in response to LPS, but may contribute as secondary producers of cytokines involved in the cytokine cascade elicited by LPS injection.