Role of cytokines in Campylobacter jejuni infection and immunity in mice

Abstract

Cytokines incorporated into agarose blocks and implanted subcutaneously into mice established an in vivo gradient which can be used to mimic a local inflammatory process. A model was developed in which cellular influx into cytokine impregnated blocks paralleled the normal cellular reaction to infections or wounds. Agarose blocks containing antigens of the intestinal pathogen, C. jejuni, were implanted in normal and infected mice. Kinetics of cellular influx into the blocks showed an early influx of lymphocytes in infected mice only. The two groups showed similar but discrete patterns of cytokine secretion within the blocks. Infected, but not normal mice, were actively synthesizing antibodies to C. jejuni at the local site (within the blocks), whereas the levels of total immunoglobulin were similar for the two groups. The results suggested that the agarose block model can be successfully applied to study local cytokine production and the role of various cells in infectious diseases. The primary infection with C. jejuni in mice resulted in the generation of sensitized B and T cells which could be boosted by rechallenge with homologous bacteria. These results indicated the presence of a functional immunity to C. jejuni challenge in mice. An antibody secreting cell assay allowed the early detection of specific antibody producing cells in circulation. In addition, data suggested a homing pattern of B cells to spleen as well as Peyer's patches. The profile of cytokine production at a local site (intestine) and in the circulation is suggestive of a role of local IL-1 and local as well as systemic IL-6 in immunity and in the pathogenesis of Campylobacter. Crude cytokine suspensions, when fed orally before challenging with C. jejuni, reduced the bacterial load from the gut and also augmented both humoral and cellular immune responses to the bacterial antigens. Oral treatment of mice with rIL-6 had an immediate effect in reducing the bacterial load whereas this effect was delayed in mice treated with rIL-5. Although IL-6 and IL-5 enhanced local as well as systemic antibodies to C. jejuni, these provided only a partial protection from rechallenge with homologous bacteria. On the other hand, mice treated with rIL-2 before challenge had better protection and a faster clearance of bacteria from their guts. In none of the groups could DTH to bacterial antigens be demonstrated, however, the lymphocytes responded to in vitro by stimulation with the same antigens. The data suggested that various cytokines have potential for use as immune modifiers to enhance the immune response to various enteric pathogens. (Abstract shortened with permission of author.)