Neuropeptide Denervation Alters Both the Elicitation and Induction Phases of Contact Hypersensitivity in Mice

• Published in: Toxicology and applied pharmacology 1998-12, Vol.153 (2), p.243-249
• Main Authors: Veronesi, B., Williams, W.C., Smialowicz, R.J., Sailstad, D.M., Doerfler, D., Selgrade, M.J.K.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn - physiology; Biological and medical sciences; Capsaicin; Cell Division; Chemical and industrial products toxicology. Toxic occupational diseases; contact hypersensitivity; Cytokines - secretion; Denervation; Dermatitis, Contact - etiology; Dinitrofluorobenzene; Ear - physiology; Female; Flow Cytometry; Lymph Nodes - physiology; Lymphocytes - classification; Lymphocytes - physiology; Medical sciences; Mice; Mice, Inbred BALB C; neurocutaneous axis; neuropeptides; Neuropeptides - physiology; sensitive subpopulations; Sensory Deprivation - physiology; substance P; susceptible populations; tachykinins; Tachykinins - physiology; Toxicology; Various organic compounds
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1998.8539

The effects of permanent disruption of neuropeptide transmission on the induction (i.e., sensitization) and elicitation (i.e., challenge) phases of contact hypersensitivity (CHS) are described. BALB/c mice were chemically denervated of neuropeptide (i.e., tachykinin) containing sensory C fibers by an acute injection of capsaicin (50 mg/kg) on postnatal day (PND) 2 to 3. As young adults (PND 45–60), these mice and their control littermates were sensitized by topical application of 0.1% 2,4-dinitrofluorobenzene (DNFB) or vehicle. Treatment groups generated from this exposure regimen consisted of untreated, controls (O/O), denervated, controls (CAP/O), untreated, sensitized (O/DNFB), and denervated, sensitized (CAP/DNFB). The elicitation phase of CHS was evaluated in these animals by measuring ear thickness in response to a DNFB challenge. In DNFB-sensitized groups, ear thickness was significantly increased over controls but was additionally increased 2.4-fold in CAP/DNFB compared to O/DNFB mice. The induction phase of CHS was next assessed in young adult mice by measuring lymph node cell (LNC) proliferation. For this, mice were sensitized for 3 consecutive days before their draining, auricular nodes were removed. The LNC were dissociated and cultured for 24 h with tritiated thymidine to assess LNC proliferation. As expected, significantly higher numbers of LNC occurred in both DNFB-sensitized groups (CAP/DNFB, O/DNFB) compared to the unsensitized, controls (CAP/O, O/O). However, LNC proliferation in CAP/DNFB was significantly higher than O/DNFB animals. Flow cytometry on similarly exposed mice failed to demonstrate any significant difference in the population of CD4CD8 or CD3CD45R LNC cells from neuropeptide-denervated (CAP/O, CAP/DNFB) mice or their respective treatment mates (O/O, O/DNFB), suggesting that alterations in T or B cell populations did not underlie these changes. Finally, cytokine release from the LNC from these treatment groups was examined. For this, the auricular lymph nodes were removed from animals, 2 to 4 h after the animals were administered a single application of a sensitizing concentration (0.1%) of DNFB or acetone vehicle. LNC, dissociated from these nodes, were cultured for 24 h. The nutrient media was removed from these cultured cells and examined for the release of proinflammatory cytokines, interleukin (IL)-1β, IL-2 and tumor necrosis factor (TNF)α, by ELISA. There were no significant increases in IL-2. However, IL-1β release was