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.