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Intravenous immunoglobulin reduces the ischemia/reperfusion-induced renal injury by increasing insulin-like growth factor-I production in mice
© BioMed Central Ltd 2008
Published: 13 March 2008
Sensory neurons release calcitonin gene-related peptide (CGRP) upon activation. We have previously reported that activation of sensory neurons increases insulin-like growth factor-I (IGF-I) production, thereby reducing ischemia/reperfusion (I/R)-induced liver injury in mice. Although immunoglobulin has been shown to reduce organ failures by attenuating inflammatory responses in various animal models of sepsis, its therapeutic molecular mechanism(s) is not fully understood. Since sensory neurons have an Fcγ receptor, it is possible that intravenous immunoglobulin reduces reperfusion-induced renal injury by increasing IGF-I production through sensory neuron activation. We examined this possibility in the present study.
The right renal vessels were clamped in wildtype (WT) and congenital αCGRP-deficient mice (CGRP-/-) for 45 minutes after left nephrectomy. Intravenous immunoglobulin (IVIg) (100 mg/kg) was administered immediately before ischemia (pretreatment) or 15 minutes after reperfusion (post-treatment).
Both pretreatment and post-treatment with IVIg reduced I/R-induced renal injury and enhanced increases in renal tissue levels of IGF-I in WT mice. In contrast, neither pre-treatment nor post-treatment with IVIg showed any therapeutic effects in CGRP-/- mice. Reperfusion-induced apoptosis of renal tubular cells was markedly suppressed by IVIg in WT mice, but not by IVIg in CGRP-/- mice. Pretreatment with anti-IGF-I antibody completely reversed the therapeutic effects of IVIg in WT mice. Both CGRP and IGF-I showed therapeutic effects similar to those of IVIg in WT and CGRP-/- mice. Although the F(ab') fragment of IgG did not increase CGRP release from cultured dorsal root ganglion neurons, the Fcγ fragment increased CGRP release from cultured dorsal root ganglion neurons in vitro. Administration of the Fcγ fragment significantly reduced renal injury in WT mice, while the F(ab') fragment of IgG did not.
These observations strongly suggested that IVIg might reduce reperfusion-induced renal injury by enhancing IGF-I production through prevention of renal tubular cell apoptosis. The therapeutic effects of IVIg might mainly depend on the Fcγ fragment that is capable of activating sensory neurons.
This article is published under license to BioMed Central Ltd.