Immunization with endotoxin stimulates the production of specific antibody, however it does not provide the high level of specific protection conferred by the exotoxins. In addition to their antigenic activity, endotoxins elicit other characteristic reactions which are extensive and varied. Such effects may influence host resistance more significantly than does the stimulation of specific antibody. A non-specific increase in resistance to infection with various bacterial pathogens and a reduction or elimination of such reactions as fever, Shwartzman phenomena or lethality have been shown to follow injection of endotoxin. This altered host reactivity usually is of short duration and is independent of demonstrable antibody. Although the mechanisms of such resistance have remained obscure for many years, recent studies on the humoral and cellular alterations in the host which follow the administration of endotoxins may provide meaningful information.

THE antibacterial activity of glucose oxidase1–3 and xanthine oxidase4,5 was reported twenty-five years ago. The antibacterial effect was attributed to the H2O2 generated during aerobic oxidation of an appropriate substrate. Considering the potency and broad spectrum of the antibacterial action of these enyzmes, it is surprising that attention has not been focused on them or on other flavoproteins as agents in host defence. In this report, the bactericidal action of L-amino-acid oxidase is examined.

THE term leukin was proposed almost 60 years ago to denote a class of granulocytic antibacterial agents selectively active against Gram positive bacteria1. During the past decade, sufficient progress has been made to indicate the potential significance in host defence of such bactericidal agents. Knowledge of the chemical nature of a potent leukin present in rabbit neutrophiles first emerged in 1956. On the basis of high arginine (17 per cent) and low lysine (4.5 per cent) content, this leukin was considered to be a protamine derivative2. It was subsequently shown that bacteria undergoing dissolution within developing inflammatory lesions become progressively coated with a highly basic arginine-positive substance3, which is probably delivered to the bacterial surface during phagocytosis. Leucocytic granules, which contain the bulk of the bactericidal agent4, appear to fuse with phagocytic pouches containing bacteria and to release their contents into these pouches during degranulation5,6. Such a highly localized intracellular delivery system is probably most important because highly basic proteins or polypeptides would be neutralized and rendered less effective in an extracellular milieu. It is interesting that granulocytes from patients with an X-linked granulomatous disease seem to phagocytose normally but do not kill ingested bacteria7. The leucocytic defect is apparently related to improper degranulation rather than to a deficiency in the bactericidal agent8.

Immunization with endotoxin stimulates the production of specific antibody, however it does not provide the high level of specific protection conferred by the exotoxins. In addition to their antigenic activity, endotoxins elicit other char- acteristic reactions which are extensive and varied. Such effects may influence host resistance more significantly than does the stimulation of specific antibody. A non-specific increase in resistance to infection with various bacterial patho- gens and a reduction or elimination of such reactions as fever, Shwartzman phenomena or lethality have been shown to follow injection of endotoxin. This altered host reactivity usually is of short duration and is independent of

INTRODUCTION it readily inactivated by the simple procedure of Observations by many investigators during dialysis against distilled water (25). Buchner the last fifteen years of the 19th century demonnamed this serum bactericidal substance "alexin" strated the existence of antimicrobial substances (Greek, to ward off) in 1891 (26). Since these in blood, leucocytes and lymphatic tissues. Since early reports many investigators have added to the turn of the century many tissues have been the knowledge of this material. shown to contain factors inimical to microorganIn 1905-6 Ehrlich proposed the name "compleisms. No doubt many of the recent findings ment" in place of his earlier term "addiment" to represent rediscoveries of agents which previously apply to the heat labile normal serum substance

A method has been described for the preparation of a potent antibacterial factor from rabbit polymorphonuclear leucocytes. Upon characterization, the factor was found to possess many properties in common with basic proteins. The amino acid analysis revealed that it contained a relatively large amount of arginine (17 per cent) and small amounts of the other two basic amino acids. It has therefore been identified as a protamine or protamine derivative. The leucocyte factor was very active against all Gram-positive pathogens tested but exhibited little or no action against Gram-negative species. A possible explanation of this phenomenon has been discussed. The factor was very heat-stable at acid and neutral pH and its staphylococcidal activity was blocked by glutamyl polypeptide, hyaluronic acid, and desoxyribonudeic acid. Because of the apparent similarity of the product studied here to other poorly defined leucocyte factors which had been termed leukins in the early literature, it is suggested that the name leukin be retained for it. The possible significance of this leukin in natural immunity has been discussed.