To specify the role of individual
cytokines in the immune response to
pyrogens, isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used for the experiments. Different
pyrogens (
lipopolysaccharide from Escherichia coli - LPS and live Borrelia afzelii) were applied and the time course of changes in concentrations of different
cytokines in the medium was followed using the ELISA method. It was found that nonstimulated human PBMC proliferate under in vitro conditions and produce
IL-6,
TNF-alpha,
IL-10 and finally also IL-1beta. Productions of
IL-12 and INF-gamma are not changed. Proliferation of PBMC is potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS increase the net production (stimulated minus unstimulated) of IL-1beta and
TNF-alpha significantly, while production of
IL-6 was smaller. A delayed increase in the production of
IL-10 was also observed. Productions of
IL-12 and INF-gamma were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia, increases also the production of
IL-12 and IFN-gamma, besides IL-1beta,
TNF-alpha,
IL-6 and
IL-10. Productions of IL-1beta,
IL-6 and
TNFalpha increased immediately after incubation with both LPS and Borrelia, while productions of
IL-12 and INF-gamma begin to increase 8 hours and production of
IL-10 12 hours after stimulation. Data indicate that stimulation with different
pyrogens may activate the cells of the immune cascade in a different way. Stimulation of
BPMC by LPS seems to activate the initial steps of the immune response (macrophages and granulocytes) only, while
infection with live Borrelia also stimulates the later phase of the immune response, probably due to effect of initially produced
cytokines.