DIFFERENTIAL INDUCTION OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES IN WHOLE-BLOOD BY BACTERIA - EFFECTS OF ANTIBIOTIC-TREATMENT

The in vitro production of interleukin-1 beta (IL-1 beta, IL-6, and th e IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation wi th different bacterial strains was measured to study the possible rela tionship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphyl ococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and S treptococcus pyogenes induced the cytokines IL-1 beta, IL-6, and IL-1r a, Gram-negative bacteria induced significantly higher levels of proin flammatory cytokine production than gram-positive bacteria, These diff erences were less pronounced for the anti-inflammatory cytokine IL-1ra , In addition, blood was stimulated with E. coli killed by different a ntibiotics to study the effect of the antibiotics on the cytokine-indu cing capacity of the bacterial culture, E. coli treated with cefuroxim e and gentamicin induced higher levels of IL-1 beta and IL-6 productio n but levels of IL-1ra production similar to that of heat-killed E. co li, In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killi ng showed a decreased or similar level of induction of cytokine produc tion as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.