Unregulated inflammation shortens human functional longevity

Inflamm Res. 2000 Nov;49(11):561-70. doi: 10.1007/s000110050632.


Systemic inflammation, represented in large part by the production of pro-inflammatory cytokines, is the response of humans to the assault of the non-self on the organism. Three distinct types of human ailments - namely autoimmunity, presenile dementia (Alzheimer's disease), or atherosclerosis - are initiated or worsened by systemic inflammation. Autoimmunity is unregulated hyperimmunity to organ-specific proteins, inducing rapid turnover of antigen-specific T cells of the acquired immune system with ultimate exhaustion and loss of acquired immunity IL-2 and IFN-gamma production and proliferative decline, conforming to the limited capacity of clonal division (Hayflick phenonmenon). In Alzheimer's disease (AD), the primary degenerative process of amyloid-beta (AJ3) protein precedes a cascade of events that ultimately leads to a local "brain inflammatory response". Unregulated systemic immune processes are secondary but important as a driving-force role in AD pathogenesis. Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages indicate a local immunologic activation in the atherosclerotic plaque that may be secondary to unregulated pro-inflammatory cytokines too. The premature hyperimmunity of autoimmunity, the local "brain inflammatory response" to A/3 protein in AD, and the immune response to fatty changes in vessels in atherosclerosis all signal the critical importance of unregulated systemic inflammation to common neurological and cardiovascular disease that shortens the nominal longevity of humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / immunology*
  • Arteriosclerosis / immunology*
  • Arthritis, Rheumatoid / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmunity
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / immunology
  • Humans
  • Inflammation / immunology*
  • Longevity / immunology*
  • Lymphocyte Activation
  • Multiple Sclerosis / immunology
  • T-Lymphocytes / immunology


  • Cytokines