Aspects of the relationship between irradiation injury and mammalian host defenses.

1. Whole body x-irradiation of rabbits with doses of 650 r more results in a depression or loss of serum bactericidal action. 2. Total body irradiation of rats (600 r) and guinea pigs (350 r) results is in suppressed serum bactericidal action. This post irradiation depression in serum bactericidal function in rats and guinea pigs was not as great as that observed in rabbits. 3. Following exposure to total body irradiation with doses as great as 1200 r, serum exhibits normal bactericidal action one day after irradiation. X-irradiated rabbits usually maintain normal serum bactericidal activity until the third or fourth post-irradiation day. Practically all rabbits develop suppressed serum bactericidal action by the sixth post-irradiation day. The period when most animals lose normal serum bactericidal function is between the fourth and sixth post-irradiation day. 4. With irradiation doses of 650 to 700 r, bactericidal action returns to normal by the nineteenth or twentieth post-irradiation day. 5. When a second x-irradiation exposure is administered, rabbits lose serum bactericidal action sooner and such action is suppressed for longer periods of time than after the initial irradiation. 6. The loss or suppression of the normal bactericidal activiaty of rabbit serum following 650 to 725 r of whole body x-irradiation was not demonstrated to be due to a substance in the sera of irradiated rabbits which inhibits normal bactericidal activity. No decrease in the bactericidal action of normal serum was observed following the addition of serum from x-irradiated rabbits to normal serum. 7. Titrations were carried out with sera from non-immunized x-irradiated and control rabbits to determine natural agglutinin levels. Suspensions of sheep read blood cells and Bacillus subtilis were employed as antigens. The amount of circulating natural agglutinin was not significantly altered in the sera of x-irradiated rabbits with suppressed bactericidal activity. 8. Complement concentrations determined at a time when the sera from irradiated rabbis showed suppressed bactericidal activity were of the same magnitude of x-irradiated and control rabbits. 9. Addition of either E or M fractions of guinea pig complement failed to restore the bactericidal activity of sera from x-irradiated rabbits. 10. The post-irradiation (650 r total body x-irradiation) suppression of serum bactericidal action is greatest and takes place at a time when blood platelets and leucocytes are at their lowest values. A fairly close correlation exists between loss and return of both platelet numbers and bactericidal action when group analysis is carried out. NO such correlation was observed with individual animals. 11. Total body x-irradiation results in a decrease in intracellular digestion of Candida guilliermondi by mouse phagocytes. This suppressed digestive action cannot be demonstrated 2 days after irradiation but is evident on the sixth and fourteenth post-irradiation days. 12. Cortisone treatment in doses of 0.25 to 2.5 mg daily for 4 days following total body exposure to 450 r resulted in shorter survival time and increased mortality in mice. The larger dose of hormone yielded higher mortality rates. Streptomycin treatment (6.0 mg for 25 days) decreased mortality in both the hormone and non-hormone treated mice. Streptomycin alone was more effective than streptomycin plus cortisone in protecting against the lethal effects of 450 r whole body x-irradiation. Streptomycin and cortisone, alone or in conjunction, failed to significantly change either the time of death or cumulative mortality following 700 r of whole body irradiation. 13. Polylmyxin survival times of mice following 450 r and 700 r of total x-irradiation. The decrease in mortality observed in the polymyxin treated irradiated (450 r) mice was comparable to that obtained by streptomycin treatment. 14. Piromen injected on the first post-irradiation day and every four thereafter in doses of 2.5, 5, and 10 micrograms had not beneficial effect on the survival of mice exposed to 450 r or 600 r of total body x-irradiation. 15. DNA administration resulted in decreased survival times and increased mortalities following irradiation treatment. 16. The post-irradiation mortality was not significantly different with mice exposed to 450 r when irradiation was administered at a time when local anoxia was produced in one or two legs of the mouse. 17. Pretreatment of mice with serum from normal or x-irradiated mice was without effect on survival time or total mortality following exposure to one or two doses of 450 r. 18. Serum from a normal or an x-irradiated rabbit was without effect on survival time when given in 0.1 ml amounts daily for the first five days following exposure to 600 r of total body x-irradiation.