Abstract
Sensitization of mast cells with SPE-7 anti-DNP-IgE alone initiates inflammatory cytokine production in vitro. In contrast, ε26 anti-DNP IgE does not induce inflammatory cytokines independent of antigen-stimulation. We tested these two anti-DNP IgE clones in our model of murine thermal hyperalgesia. We found pronounced hind paw hyperalgesic responses lasting to at least 6 hours following antigen challenge 24 hours after sensitization with SPE-7 but not ε26. SPE-7/DNP did not induce greater levels of mast cell degranulation in the hind paw. Differential hyperalgesic responses were accompanied by otherwise equivalent inflammatory changes measured including histamine release, neutrophil influx, expression of TNF-α, IL-1β, and IL-6 genes and changes in levels of TNF-α, IL-1, and IL-6 proteins. Inflammatory responses and hyperalgesia were dependent on antigen challenge and were not detected in sham-challenged mice. Hyperalgesia responses or other inflammatory changes were not detected in the hind paw tissue post-sensitization in the 24 hours prior to antigen challenge. We demonstrate a novel behavioral, antigen-dependent difference between reactions mediated by these IgE antibody clones in vivo in mice. We are currently further investigating the inflammatory cytokine milieu and measuring changes in mRNA and protein levels of nociceptive signaling molecules provoked by IgE/Ag-induced cutaneous anaphylaxis to elucidate the mechanisms underlying this differential pain outcome.