Capsaicin-sensitive primary sensory neurons are potent modulators of murine delayed-type hypersensitivity reactions.
Capsaicin, a neurotoxin that depletes primary sensory neurons (polymodal nociceptors) of neuropeptides, was used to explore the role of such neurons on the expression of delayed-type hypersensitivity reactions in mice. BALB/c mice received s.c. injections with capsaicin (100 mg/kg) and tested 1 to 2 wk later exhibited insensitivity to chemically induced irritation (greater than 80% reduction in the eye-wiping response for more than 15 wk) as well as loss (greater than 95% reduction) of the ear swelling response to topical capsaicin. Early (less than or equal to 4 h) ear swelling to topical DNFB and oxazolone was also markedly reduced by capsaicin pretreatment, suggesting neurogenic inflammation as a major component of the early irritant reaction to haptens. In contrast, capsaicin-pretreated mice exhibited enhanced contact sensitivity (CS) reactions to oxazolone (greater than 90%) and DNFB (greater than 50%) and enhanced delayed-type hypersensitivity reactions to SRBC (greater than 20%). Adoptive transfer experiments revealed that CS augmentation was not due to generation of increased numbers and/or activity of effector T cells. Histologic studies as well as experiments measuring migration of 51Cr-labeled, Ag-nonspecific cells showed increased edema and enhanced cell localization in CS elicitation sites in capsaicin-pretreated mice. These results indicate that peptidergic neurons, via neuropeptide release, regulate the expression of T cell-mediated, delayed-in-time, cutaneous inflammatory reactions. The net effect of these neurons on the late (cellular) phase of such responses seems to be suppressive, because their impairment results in augmented reactions.
Girolomoni
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Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235.
Tigelaar
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D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000209:etiology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D008198:Lymph Nodes / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009475:Neurons, Afferent / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology; D010146:Pain / Q000503:physiopathology
D009479:Neuropeptides; D002211:Capsaicin