Effect of bee venom on experimental arthritis.

Stimulation of cells and tissues, whether by mechanical, hormonal, or neurological means, results in the increased biosynthesis of prostaglandins (Ramwell and Shaw, 1970). It has been suggested that one such stimulus is inflammation, in the course of which phospholipases are freed from the lysosomes of phagocytes. These enzymes can cleave phospholipids of the cell membrane to yield arachidonic acid, which is in turn converted to prostaglandins by freely available tissue enzymes (Anderson, Brocklehurst, and Willis, 1971). Phospholipases are also among the most active components of a number of animal venoms (Eliasson, 1959), such as bee venom and snake venom, which both contain phospholipase A and appear to release prostaglandins from tissues (Vogt, Meyer, Kunze, Lufft, and Babilli, 1969). Since it has been observed that prostaglandin E1 (PGE,) prevents and suppresses adjuvant arthritis in rats (Zurier and Quagliata, 1971), it was considered possible that injections of venom in rats with adjuvant disease might have an effect similar to that of treatment with prostaglandins. Because of its venerable position in the medical and folk lore of Europe and Asia, the venom of the honey bee (Apis mellifera) was used. Bee sting or bee venom therapy has been reported to be effective in treatment of the rheumatic diseases (Maberly, 1910; Beck, 1935), and is widely used, even at the present time, in many regions of the U.S.S.R. (Zaitev and Poriadin, 1964). Adjuvant disease in the rat includes a severe and persistent polyarthritis, which appears 10 to 14 days after a single intradermal injection of complete Freund's adjuvant (Pearson and Wood, 1959) and is widely accepted as a useful animal model of human disease. The data obtained in these studies indicate that treatment of rats with whole bee venom from the time of adjuvant injection does in fact suppress adjuvant arthritis, whereas treatment with the known fractions of bee venom alone (including phospholipase A) does not reduce the inflammatory response. When treatment is delayed until arthritis appears, bee venom treatment does not alter the course of disease. Injections ofwhole beevenom result in rapid elevation ofserum corticosterone concentration and bee venom therapy does not prevent arthritis in adrenalectomized rats. The findings suggest that bee venom suppression of adjuvant arthritis is mediated, at least in part, through adrenal gland stimulation. These observations stand in contrast to the findings that PGE1 suppresses adjuvant arthritis in adrenalectomized rats and therefore suggest that the effects of bee venom are not necessarily related to the release of prostaglandins.