Abstract
One proposed mechanism by which alum enhances an immune response is by its ability to induce an inflammatory response that results in the release of uric acid from necrotic cells. Uric acid is thought to be a mediator in enhancing the immune response. The aim of this study was to investigate the immunopotentiating effect of uric acid. Groups of BALB/c mice were injected intraperitoneally with ovalbumin, ovalbumin + alum, ovalbumin + uric acid, uric acid, alum, or allopurinol. Two other groups were pretreated with allopurinol and were given ovalbumin + alum, or ovalbumin + uric acid 24 hours later. An additional two groups served as controls. On days 4, 7 and 10 post-injection, the numbers of Interleukin 4(IL-4) and Interferon-γ (IFN-γ) secreting spleen cells were determined by the ELISPOT assay. Serum uric acid levels were determined using an autoanalyser and nitric oxide using the Greiss reagent. The groups that received alum + ovalbumin or uric acid + ovalbumin had the highest numbers of IL-4 and INF-γ secreting cells as compared to all the groups. Allopurinol administration one day prior to alum + ovalbumin or uric acid + ovalbumin resulted in a decrease in the number of IL-4 and INF-γ secreting cells when compared to alum+ ovalbumin or uric acid + ovalbumin allopurinol - untreated groups. Groups that received alum, alum + ovalbumin, uric acid, and uric acid + ovalbumin had high serum uric acid levels as compared to all the groups. All groups that received alum had the highest levels of nitric oxide when compared to the groups that were not given alum. In conclusion, it appears that uric acid might be a mediator in the adjuvant effect of alum.
Highlights
Alum is the most widely used adjuvant in human and veterinary vaccines [1,2]
Several potential mechanisms are commonly cited to explain the method of action of this adjuvant: One proposed explanation is that alum can potentiate the immune response by retaining the antigen at the injection site suggesting a sustained release of antigen leading to the recruitment of Antigen Presenting Cells (APCs)
In view of the fact that one of the potential explanations for the adjuvant effect of alum is through the induction of inflammation, which can result in uric acid (UA) release from necrotic cells; the aim of this study was to assess the role of UA in the adjuvant effect of alum
Summary
Alum is the most widely used adjuvant in human and veterinary vaccines [1,2]. Adsorption of antigen to alum is essential to enhance its immunogenicity [3]. Several potential mechanisms are commonly cited to explain the method of action of this adjuvant: One proposed explanation is that alum can potentiate the immune response by retaining the antigen at the injection site suggesting a sustained release of antigen leading to the recruitment of Antigen Presenting Cells (APCs). This is known as the depot effect [3,8,9,10].
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