HISTAMINE INVOLVEMENT IN UVB-INDUCED AND CIS-UROCANIC ACID-INDUCED SYSTEMIC SUPPRESSION OF CONTACT HYPERSENSITIVITY RESPONSES

Studies in experimental models have implicated histamine and prostanoi ds in ultra-violet B (UVB)- and cis-urocanic acid (UCA)-induced system ic immunosuppression. This study examined the hypothesis that WE irrad iation and cis-UCA suppressed contact hypersensitivity responses to ha pten by induction of histamine, which in turn evoked a prostanoid-depe ndent component of immunosuppression. BALB/c mice were administered wi th a cis-UCA monoclonal antibody, a combination of histamine types I a nd 2 receptor antagonists, or indomethacin. Mice were sensitized to 2, 4,6-trinitrochlorobenzene (TNCB) on their ventral surface 5 days after UVB irradiation, or cis-UCA or histamine administration. Ears were ch allenged with TNCB 5 days later. Cis-UCA antibody inhibited the suppre ssive effects of UVB by approximately 60% and confirmed that suppressi on of contact hypersensitivity responses by UVB was due, at least in p art, to mechanisms involving cis-UCA. Histamine suppressed contact hyp ersensitivity responses and the effects of cis-UCA and histamine were not cumulative, suggesting that cis-UCA and histamine signal largely t hrough the same pathway. The immunosuppressive effects of histamine we re not affected by the cis-UCA antibody, consistent with the model tha t histamine acts downstream of cis-UCA. Administration of histamine re ceptor antagonists and indomethacin each approximately halved the UVB- and cis-UCA-induced systemic suppression of contact hypersensitivity responses. The effects of the reagents that inhibited the action of hi stamine and prevented prostanoid production were not cumulative, and s uggested involvement in the same pathway. These results support the in volvement of cis-UCA, histamine and prostanoids, in a sequence, in UVB -induced systemic suppression of contact hypersensitivity responses.