Highly cytokinergic SPE-7 anti-dinitrophenyl-immunoglobulin E induces antigen-dependent thermal hyperalgesia and inflammatory cytokine production in the mouse hindpaw (P6000)

Abstract

Abstract SPE-7 anti-DNP-IgE initiates inflammatory cytokine production without antigen stimulation in vitro. In contrast, ϵ2624 anti-DNP IgE does not induce inflammatory cytokines independent of antigen-stimulation. However, their effects in vivo have not been described. We tested two well-characterized anti-mouse IgE antibody clones in our model of murine thermal hyperalgesia. We found pronounced hindpaw hyperalgesic responses lasting to at least 6 hours following antigen challenge after sensitization with SPE-7. These responses were accompanied by histamine release and neutrophil influx as we have previously shown in c48/80-mediated thermal hyperalgesia. In contrast, we found that antigen challenge following sensitization with clone ϵ2624 produced slight hyperalgesia at 1 hr that was resolved by 3 hours. We demonstrate a novel functional, behavioral difference between reactions mediated by these IgE antibody clones in vivo in mice. Also, SPE-7 does not lead to antigen-independent cytokine production in the mouse hind paw. After antigen challenge, both IgEs produce equivalent levels of TNF-α, IL-1, and IL-6, and cause equivalent histamine release and neutrophil influx. Thus tissue-resident sentinel mast cells may be critical initiators of allergen-evoked hyperalgesia in mice and differences in the nature and repertoire of IgE antibodies produced during an allergic response likely have pathophysiological implications for various health outcomes including pain.