Inhibition of cutaneous contact hypersensitivity in the mouse with systemic or topical spiperone: topical application of spiperone produces local immunosuppression without inducing systemic neuroleptic effects.
We tested the ability of the neuroleptic agent spiperone (8-[3-(p-fluorobenzoyl)propyl]-1-phenyl-1,3,8-triazaspiro-[4.5] decan-4- one) to influence the tissue swelling and leukocyte infiltration associated with T-cell--dependent immune responses, i.e., contact hypersensitivity reactions, in mice. Contact hypersensitivity reactions were elicited by applying the haptens oxazolone or dinitrofluorobenzene topically to one or both ears 5-8 d after epicutaneous sensitization. When spiperone was given subcutaneously at a dose of 30 or 150 mg/kg, 1 h after challenge with oxazolone, cutaneous contact hypersensitivity to this hapten was significantly diminished. When applied topically in concentrations as low as 0.08% (w/w), preparations of spiperone significantly suppressed both the tissue swelling and the leukocyte infiltration associated with the elicitation phase of contact hypersensitivity. Topical treatment with spiperone also suppressed the sensitization phase of contact sensitivity. However, mice treated topically with spiperone, unlike those treated systemically, exhibited no drowsiness or other evidence of central nervous system effects. Spiperone expresses both serotonin and dopamine receptor antagonist activity. However, unlike spiperone, the chemically unrelated serotonin antagonists, trazadone and mianserin, and the dopamine receptor antagonist, haloperidol, were not effective in suppressing contact hypersensitivity. Our results indicate that spiperone can have immunosuppressive effects on contact hypersensitivity reactions in the mouse, even when applied topically in doses that lack neuroleptic effects, and that the mechanism of action of spiperone on the immune response may be independent of its serotonin or dopamine receptor blocking properties.
Sharpe
R J
RJ
Department of Dermatology, Beth Israel Hospital, Boston, MA 02215.
Chandrasekar
A
A
Arndt
K A
KA
Wang
Z S
ZS
Galli
S J
SJ
D000287:Administration, Topical; D000818:Animals; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D018492:Dopamine Antagonists; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012702:Serotonin Antagonists; D013134:Spiperone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
D018492:Dopamine Antagonists; D007166:Immunosuppressive Agents; D012702:Serotonin Antagonists; D013134:Spiperone