The role of leukotriene D4 as a mediator of allergic conjunctivitis in the guinea-pig.

The role of leukotriene D4 (LTD4) as a mediator of conjunctival microvascular permeability changes associated with immediate hypersensitivity reactions in the guinea-pig conjunctiva has been investigated using two novel, selective LTD4 receptor antagonists, L-648,051 and L-649,923. Changes in microvascular permeability were measured through the accumulation of [99mTc]albumin. LTD4 administered intravenously produced dose-related increases in conjunctival microvascular permeability through a mechanism which does not involve the generation of prostaglandins as indicated by the failure of indomethacin to attenuate the response. The response to LTD4 was significantly blocked by the receptor antagonists, L-648,051 and L-649,923. Topical application of antigen (either single challenge or 2 challenges separated by 24 h) to the eyes of sensitized guinea-pigs caused significant increases in conjunctival microvascular permeability. Following a single challenge, the antigen response was largely blocked by mepyramine (H1 receptor antagonist), but was unaffected by L-648,051 and L-649,923. Following a second challenge (24 h later) a substantial portion of the response was inhibited by L-648,051 and L-649,923. Indomethacin failed to inhibit either challenge. These results suggest that LTD4 may have a role in chronic allergic conjunctivitis.