Age-dependent differential development of leukotactic and vasoactive responsiveness to acute inflammatory mediators

Age-associated development of increased cutaneous vascular permeability and neutrophil accumulation in response to several inflammatory mediators was examined in young rabbits. The development of increased cutaneous vascular permeability was mediator-, age- and dose-dependent and was potentiated by prostaglandin E₂ (PGE₂). While 4-week-old rabbits responded to bradykinin, they did not develop increased vascular permeability in response to histamine, acetyl glyceryl ether phosphocholine (AGEPC). N-formyl-methionyl-leucyl-phenylalanine, or zymosan-activated plasma at doses which induced significant increases in vascular permeability in 13-week-old rabbits. Dose-dependent increases in vascular permeability after intracutaneous injection of AGEPC and histamine were observed by 6 weeks of age although fewer animals responded to histamine as compared to AGEPC. In addition, coadministration of PGE₂ allowed the expression of increased vascular permeability to AGEPC, N-formyl-methionyl-leucyl-phenylalanine and zymosan-activated plasma in all 4-week-old animals. Interstitial neutrophil accumulation as well as increased vascular permeability was also age-, time-, mediator- and dose-dependent. Compared to 13-week-old rabbits, fewer numbers of interstitial neutrophils were observed in 4-week-old animals for up to 4 hours after intracutaneous injection of AGEPC. PGE₂ potentiated the neutrophil response to N-formyl-methionyl-leucyl-phenylalanine and zymosan-activated plasma in both young and adult rabbits; nevertheless, the response in young animals was never as extensive as in the adult animal with the exception of the neutrophil infiltrative response after administration of AGEPC and PGE₂. These results suggest that PGE₂ synthesis and/or reactivity in young animals may be significantly different from adult animals and in part may account for the lowered reactivity to acute inflammatory mediators in the young animal.