COMPARATIVE EFFECTS OF CORTICOSTEROIDS ON HOST RESISTANCE TO INFECTION IN RELATION TO CHEMICAL STRUCTURE

Abstract

In a comparative study concerning the effect of corticosteroids on host resistance to infections, five compounds were found to decrease host resistance, while three did not have this property, although all eight compounds were highly antiinflammatory. The compounds capable of decreasing host resistance were (I) hydrocortisone acetate; (III) 9α-fluoro, 16α-methylprednisolone acetate; (IV) 9α-fluoro, 16α-hydroxyprednisolone; (V) 9α-fluoro, 16α-hydroxyprednisolone, 16α–17α-acetonide; and (VII) 9α-fluoro, 16α-hydroxypredmsolone, 16α-, 17α-acetonide, 21 disodium phosphate. Following a single injection of 10 mg of any of these compounds, latent corynebacterial infection was provoked into active pseudotuberculosis. Also, mice injected with these corticosteroids were more susceptible to infection with Corynebacterium kutscheri, Staphylococcus aureus, Klebsiella pneumoniae, or Listeria monocytogenes. These same corticosteroids inhibited the ability of mouse peritoneal macrophages to spread on glass surfaces. The three compounds incapable of decreasing host resistance, although highly antiinflammatory, were: (II) 6α-methylprednisolone, 21 sodium hemisuccinate: (VI) 9α-fluoro, 16α-hydroxyprednisolone, 16α-, 17α-acetonide, 21 hemisuccinate; and (VIII) 9α-fluoro, 16α-hydroxyprednisolone, 16, 21 dihemisuccinate. These three compounds were also unable to inhibit the spreading of macrophages on glass. The importance of succinate group bound to the corticosteroid molecule as hemisuccinate is emphasized since it is seen that the infection-provoking property can be dissociated from the antiinflammatory property. This finding may be of practical consequence in selecting a corticosteroid for treatment in disease, and also shows that one cannot use, indifferently, corticosteroids only on the basis of their common antiinflammatory property.