Specific Inhibition of Allergic Reactions to Penicillin in Man by a Monovalent Hapten

Abstract

The principle of specific hapten inhibition is classically used to demonstrate antibody specificity in vitro. The purpose of the reported studies was to investigate whether this principle may also be used to inhibit specifically clinical allergic reactions to penicillin in vivo, in experimental animals and in man. Studies in vitro indicate that a synthetic penicilloyl hapten (benzylpenicil-loylformyllysine, BPO-FLYS) is highly efficient in blocking anti-penicilloyl antibodies, as revealed by inhibition of precipitation, haemagglutination, complement fixation and the Schulz-Dale reaction. BPO-FLYS is also capable of inhibiting in vivo passive cutaneous and systemic anaphylaxis in guinea-pigs and wheal-and-erythema skin reactions to penicilloyl-polylysine in man. Extensive toxicologic studies indicate that BPO-FLYS may be tolerated in large doses in man. Competition experiments in vitro also show that it does not interfere with the antibiotic activity of penicillin.

Isolation of a Purified Allergen from Kentucky Blue Grass Pollen

“…These univalent compounds would then be expected to bind to the Fab regions of the IgE antibodies and thus inhibit the combination of IgE antibod ies with the offending multivalent aller gen^). The feasibility of this approach gains support from the successful regimen devel oped by de Week [10] for the treatment of penicillin allergy by the injection of large doses of the univalent penicillin derivative, benzylpenicilloyl-formyl lysine, prior to ad ministration of penicillin to sensitive pa tients.…”

Modulation of the IgE Antibody Response in Rats to Kentucky Blue Grass Pollen Allergens

“…The use of allergens complexed to adsorbents, such as aluminum hydroxide or tyrosine [14], for hyposensitization therapy -at one time be lieved to lead to dramatic clinical improve ments -has not resulted in striking break throughs. On the other hand, penicillin al lergy, which is triggered by this chemically well-defined antibiotic, has been managed by inhibiting the reaction between the tissue fixed anti-penicillin reagins and the corre sponding multivalent antigen(s) by the ad ministration of an appropriate univalent penicillin derivative, benzylpenicilloylformyl-L-lysine [6]. Similarly, it was dem onstrated earlier in this laboratory that the aqueous extract of ragweed pollen con tained hapten-like constituents capable of inhibiting the Prausnitz-Kiistner reaction, which was inducible with the high molecular weight multivalent components of ragweed pollen [1].…”

Molecular Mechanisms of T and B Lymphocyte Triggering

“…Whereas stimulation by BPN and BPO lymphocytes could not be inhibited by the monovalent hapten BPO-formyl-lysine [7] even in 100-fold excess, inhibition of BPO-PLL stimulation was quite marked in some cases. This could sug gest that cells stimulated by the plurivalent BPO-PLL antigen are essen tially B lymphocytes, which may readly be inhibited by the corresponding monovalent BPO hapten.…”