Depression of phagocytosis by sulfamethazine.

Studies in our laboratories (D. Coffin, D. Gardner, and R. Holzman, Arch. Environ. Health, 16:633, 1968) have shown that air pollutants depress the phagocytic ability of the pulmonary alveolar macrophages (PAM) in rabbits. During the course of these studies, sulfamethazine was administered to some of these animals. It was noted that PAM of sulfamethazine-treated rabbits ingested fewer bacteria than those of untreated animals. The fact that sulfonamides affect the process of phagocytosis is not widely known. A recent authoritative pharmacological text (J. DiPalma (ed.), Drill's Pharmacology in Medicine, 3rd ed., McGraw-Hill Book Co., New York, 1965) states, ". .9. there is no direct action on the phagocytic mechanism." A review published in 1949 (J. Berry and J. Spies, Medicine 28:239, 1949), however, cited reports of increased, decreased, and unchanged phagocytosis after sulfonamide administration. The reviewers believed that no firm conclusion could be reached. Seneca and Peer (J. Am. Geriat. Soc. 14:187, 1966) helped to clarify the situation by showing that low levels of sulfonamides enhanced and high levels depressed in vitro phagocytosis by human polymorphonuclear leukocytes. Because of renewed interest in experimental studies of the properties of macrophages, we are reporting a series of in vivo experiments showing a depression of the phagocytic ability of rabbit PAM after the oral administration of sulfamethazine. Rabbits were randomly assigned either tap water or tap water containing sulfamethazine (0.77 g/liter) ad libitum for a period of 1 week. They were then anesthetized, and 1 ml of a concentrated suspension (108 organisms) of washed 3-hemolytic, group C Streptococcus pyogenes was injected intratracheally. After 30 min, the animals were sacrificed, the trachea cannulated, and the lungs lavaged three times with warm buffered-saline solution, pH 7.2. The cells were sedimented by centrifugation,