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Melittin, a mast cell lytic agent which comprises 50% of the protein content of bee venom, may be responsible for some of the severe reactions produced by bee stings in allergic and non-allergic individuals. We therefore investigated some of the biologic properties of this molecule in mice and found that repeated intradermal injections of melittin without adjuvant induced IgE formation in mice. In addition, melittin as well as another surfactant, saponin, were potent adjuvants for IgE formation in mice when mixed with ovalbumin (Ov). Titres of 1280 and 2560 to ovalbumin were produced in CBA mice after two injections of melittin and Ov or saponin and Ov. Melittin was also shown to have an enhancing effect on the vascular permeability induced by an antigen antibody interaction in mouse skin. Evan's blue dye was injected intravenously into ovalbumin-sensitized mice which had been injected intradermally with ovalbumin alone, melittin alone or a mixture of melittin and ovalbumin. The amount of local extravasation of dye was significantly greater in the area injected with the melittin and ovalbumin mixture than the amount of dye obtained from the skin site injected with melittin alone plus that extracted from the site injected with ovalbumin alone.

It is known that heparin which is strongly anionic will precipitate in vitro with cationic proteins such as melittin, the principal constituent of bee venom. Our experiments indicate that mice immunized with complexes of melittin and heparin produced greater amounts of IgE and IgG antibody (to this protein) than did mice immunized with melittin alone. It is possible that heparin released from mast cells following a bee sting could complex with melittin and enhance the allergenic properties of this molecule.

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