Different respiratory syncytial virus and Quillaja saponin formulations induce murine peritoneal cells to express different proinflammatory cytokine profiles

The recognition of a pathogen or a vaccine antigen formulation by cells in the innate immune system leads to production of proinflammatory cytokines, which will determine the ensuing acquired immune response quantitatively an d qualitatively. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are the first set of cytokines produced upon such an encounter, which have roles both in protective immunity and immunopathogenesis evident with respiratory syncytial virus (RSV). RSV antigens in different physical adju vant-vaccine formulations were analysed for their capacity to provoke cultu red murine peritoneal cells to produce these three proinflammatory cytokine s. RSV immunostimulating complex (ISCOM), i.e. both antigen and adjuvant ar e incorporated in the same particle, induced high levels of 11-1 alpha bein g of the same magnitude or higher than those of live. RSV and lipopolysacch aride (LPS). Live virus and LPS induced higher levels of IL-6 and TNF-a tha n ISCOM and so did non-adjuvanted UV-inactivated RSV but only at high doses . ISCOM-Matrix, i.e. ISCOM without antigens, admixed as a separate entity t o inactivated RSV, downregulated or blocked the cytokine response to the in activated RSV in contrast to ISCOM. Kinetic studies showed that ISCOM induc ed cytokine production first detected at hours 1, 2, 4 for TNF-alpha, 11-6 and IL-1 alpha respectively, which was earlier than for the other antigen f ormulations containing corresponding doses of antigen and/or Quillaja adjuv ant. Peak values for production of TNF-alpha and IL-6 were at 8 h and for 1 1-1 alpha at 72 h following stimulation with ISCOM. The delayed appearance of IL-1 alpha may reflect the cell-bound nature of this cytokine. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Sci ence B.V. All rights reserved.