CYTOKINE RELEASE AS A MECHANISM MEDIATING IGIV ADVERSE REACTIONS

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T-helper type 1 immune responses are associated with IL-12, IFN( and cellular immune responses. These responses can be induced by bacteria and their products, notably, bacterial DNA (bDNA) and lipopolysaccharide (LPS). These products can stimulate macrophages to release other proinflammatory cytokines, TNFalpha and IL-1beta. Manufacture of plasma derivatives involves steps that are not aseptic and which can lead to bacterial contamination. The intact bacteria are removed by sterile filtration, but this does not remove LPS or bDNA. Thus it was of interest to see whether these bacterial products can induce cytokines that may be associated with adverse events following administration of immune globulin (Ig). Like intact bacteria bDNA induced large amounts of IL-12 and IFNgamma, but this was not the case with LPS. All three stimuli (bacteria, bDNA and LPS) induced IL-10 secretion. Kinetic analyses showed that the bacteria and bDNA induced IL-10 at the same rate as LPS. However, whereas IL-12 production peaked at 6-18 h, IL-10 production continued to remain elevated. These kinetics suggested that IL-10 may be modulating the Th1-like cytokine response to bacteria and bDNA. The relatively poor IL-12 response to LPS was enhanced in the presence of anti-IL-10 antibody. These results demonstrate that bacterial components have the ability to generate cytokines which may be involved in adverse events. They also suggest that IL-10 may dampen these unwanted responses.