INVOLVEMENT OF HISTAMINE OR TUMOR-NECROSIS-FACTOR IN EARLY-TYPE HYPERSENSITIVITY

A novel early-type hypersensitivity (ETH) reaction, manifested as capi llary congestion, increase of vasopermeability, and plasma protein lea kage, can be induced within 1 h after challenge of antigen-sensitized mice. The mediators involved in ETH varied among different strains of mice. The poly(Glu(60)Ala(30)Tyr(10)) (GAT)-induced ETH in BALB/c mice was blocked by diphenhydramine (histamine H-1 antagonist) and ketanse rine (serotonin antagonist), but not by cimetidine (histamine H-2 anta gonist). These results indicate that both histamine and serotonin are involved, and that the histamine effect is mediated through a H-1 rece ptor. Meanwhile, GAT-induced ETH in B6 mice was inhibited by anti-TNF alpha antibody suggesting that TNF alpha is involved. The mice can be classified into either histamine or TNF alpha type based on the patter n of mediator involved in ETH. A/J and CBA strains as well as BALB/c m ice were classified as histamine type while A.TL, B10.BR, and C3H/He i n addition to B6 mice were TNF alpha type. The observation that GAT-in duced ETH in (BALB/c x B6)F-1 mice was inhibited by both diphenhydrami ne and anti-TNF alpha suggests that the mediation of the actions of hi stamine or TNF alpha by GAT was genetically controlled and inherited a s the dominant trait in (BALB/c x B6)F-1 mice. ETH could be passively transferred by heat (56 degrees C, 4 h)-treated anti-GAT sera. Sera de rived from the histamine type transferred ETH across the type barrier and histamine was the mediator, irrespective of the type of the recipi ent. However, sera derived from TNF alpha type only transferred ETH to the mice of the same TNF alpha type and TNF alpha was the mediator.