Nondisposable materials, chronic inflammation, and adjuvant action

Area of Science:

• Immunology
• Cell Biology
• Pathology

Background:

• Chronic inflammatory responses and the mechanisms of immunologic adjuvants are not fully understood.
• Macrophage-lineage cells play a critical role in both chronic inflammation and adjuvant activity.
• Increased macrophage numbers in chronic inflammation may result from enhanced survival or proliferation.

Purpose of the Study:

• To present evidence for a unifying hypothesis explaining macrophage survival and proliferation in chronic inflammation and adjuvant action.
• To investigate the role of particulate materials in promoting monocyte/macrophage survival and proliferation.

Main Methods:

• Review of existing literature on materials that initiate chronic inflammation and possess adjuvant activity.
• Analysis of how macrophages interact with and process various particulate materials.
• Examination of the effects of macrophage-colony stimulating factor on macrophage proliferation in response to these materials.

Main Results:

• Many particulate materials, including oxidized low-density lipoprotein, inflammatory microcrystals, amyloidogenic peptides, and biomaterials, promote macrophage survival and proliferation.
• Adjuvants like alum, emulsions, heat-killed bacteria, and silica induce similar macrophage responses.
• Low concentrations of macrophage-colony stimulating factor can enhance proliferation beyond mere survival upon material uptake.

Conclusions:

• The accumulation of macrophages in chronic inflammation and at adjuvant sites may stem from impaired cell death pathways.
• A shift in the balance between macrophage survival and cell death can perpetuate inflammatory and immune responses.
• This mechanism offers a potential explanation for the sustained nature of chronic inflammation and the efficacy of adjuvants.