Nondisposable materials, chronic inflammation, and adjuvant action

Journal of Leukocyte Biology
John A Hamilton

Abstract

Why inflammatory responses become chronic and how adjuvants work remain unanswered. Macrophage-lineage cells are key components of chronic inflammatory reactions and in the actions of immunologic adjuvants. One explanation for the increased numbers of macrophages long term at sites of chronic inflammation could be enhanced cell survival or even local proliferation. The evidence supporting a unifying hypothesis for one way in which this macrophage survival and proliferation may be promoted is presented. Many materials, often particulate, of which macrophages have difficulty disposing, can promote monocyte/macrophage survival and even proliferation. Materials active in this regard and which can initiate chronic inflammatory reactions include oxidized low-density lipoprotein, inflammatory microcrystals (calcium phosphate, monosodium urate, talc, calcium pyrophosphate), amyloidogenic peptides (amyloid beta and prion protein), and joint implant biomaterials. Additional, similar materials, which have been shown to have adjuvant activity (alum, oil-in-water emulsions, heat-killed bacteria, CpG oligonucleotides, methylated bovine serum albumin, silica), induce similar responses. Cell proliferation can be striking, following uptake of s...Continue Reading

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