LEUKOTRIENE B-4 MODULATES IN-VIVO EXPRESSION OF DELAYED-TYPE HYPERSENSITIVITY BY A RECEPTOR-MEDIATED MECHANISM - REGULATION BY LIPOXIN A(4)

Leukotriene B-4 (LTB(4)) is a potent proinflammatory arachidonic acid metabolite whose actions are mediated by specific receptors. Recent ch aracterization of a high-affinity LTB(4) receptor on the surface of gu inea pig CD4(+) T lymphocytes prompted examination of a possible role of LTB(4) in modulating in vivo expression of delayed-type hypersensit ivity (DTH) to tuberculin (PPD). In the absence of PPD, intradermal in jections of LTB(4) or LTB(4)/LTD(4) receptor antagonists did not elici t delayed-onset erythema at 24 h. When injected together with PPD, LTB (4) (1 fmol to 1 pmol) caused a significant 25 to 30% decrease in DTH expression, whereas LTB(4) receptor antagonists SC-41930, LY-223982, O NO-4057 (0.1-10 nmol), caused a highly significant (P < .01) 25 to 50% increase. The effect of SC-41930 on DTH expression was inhibited by a 10-fmol dose of LTB(4). LTD(4) receptor antagonist LY-171883 had no e ffect on DTH expression. Lipoxin A(4) (DXA(4)) interferes with binding of LTB(4) to T lymphocytes or neutrophils by reducing LTB(4) receptor density. it caused a small but significant enhancement of DTH express ion at 1-nmol doses when injected with PPD. Lipoxin B-4 had no effect. Enhancement or inhibition of grossly visible delayed skin responses t o PPD by LTB(4), LTB(4) receptor antagonists or LXA(4), was not associ ated with qualitative or quantitative changes in superficial or deep d ermal mononuclear cell infiltrates at the reaction site. We conclude t hat LTB(4) modulates visible expression of DTH in vivo by a receptor-m ediated mechanism.