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Role of Fumaropimaric Acid in Guinea Pig Complement Dependent and Non-Complement Dependent Biologic Reactions

I. Inhibition of Forssman, Reversed Passive Arthus, and PCA Reactions by Fumaropimaric Acid¹

From the Department of Immunochemistry, Walter Reed Army Institute of Research, Washington, D. C. 20012, and the Immunobiology Branch, Armed Forces Institute of Pathology, Washington, D. C. 20305

Abstract

Fumaropimaric acid, one of a newly discovered group of potent, complement inhibitors has been shown to block the hemolytic activity of undiluted guinea pig serum when added in vitro, and after intravenous injection into guinea pigs. It also dissociates the activated trimolecular C'(5,6,7)_a complex, preventing its chemotactic activity.

When injected intravenously in doses of 600 mg/kg or less, fumaropimaric acid suppresses the complement dependent, systemic Forssman, cutaneous Forssman and reversed passive Arthus reactions. In the last reaction it was shown that complete inhibition could occur despite no interference with the formation of tissue-bound antigen-antibody complexes or the fixation of C'3 in vessel walls. Although the lysis of sensitized erythrocytes incubated with serum from guinea pigs injected with the drug was inhibited, this did not prevent the complement reaction from proceeding to and possibly through the EAC'la (4,2)a step. Thus, the ability of C'3 to be bound in sites of the Arthus reaction inhibited by fumaropimaric acid might indicate a block in the in vivo reaction beyond the C'3 step.

It is not clear, however, whether the suppression of any of these complement dependent reactions is due to the effect of fumaropimaric acid on the complement system or on some other function(s) necessary for the expression of these responses.

The PCA reaction in guinea pigs was markedly but incompletely inhibited by fumaropimaric acid. No difference was noted in the effects of the drug on the homocytotropic reaction caused by non-complement-fixing guinea pig antibodies or the heterocytotropic reaction caused by complement-fixing rabbit antibodies. In view of the evidence that guinea pig PCA given by these antibodies is not complement dependent, it is unlikely that fumaropimaric acid exerts its partial suppressive effect on the PCA by interferring with complement. Evidence is cited that makes it unlikely that the demonstrated direct antihistaminic effect of fumaropimaric acid is responsible for the suppression of the PCA.

Footnotes

¹ Part of the work was presented at 52nd Annual Meeting of the Federation of American Societies for Experimental Biology, April, 1968 (Fed. Proc., 27: 313, 1968).

² Present address: University of California Hospitals, Department of Medicine, San Francisco, California 94122. Recipient of NIH Special Research Fellowship #5 F-3 A1-31, 787-02, National Institute of Allergy and Infectious Diseases.

³ Naval Stores Laboratory, Olustee, Florida 32072.