The binary classification of chronic diseases

Abstract

Acute diseases start with an insult and end when insult disappears. If the trauma induces an immune reaction (which happens in most cases), this reaction must be terminated with some type of resolution mechanism, when the cause of the trauma ceases. Chronicity develops if insult is permanent or if the resolution mechanism is defective. Another way to reach disease chronicity is a positive feedback loop, whereby the immune reaction activates an internal, insult-like reaction. A distinction between chronic states characterized by a persistent, low suppressive effect and those characterized by a persistent, high suppressive effect of regulatory T cells (Treg), is proposed. This two-class division represents two ways to reach chronicity: (a) by maintaining inflammatory reaction long after insult disappears (“low Treg”), or (b) by suppressing inflammatory reaction prior to the disappearance of insult (“high Treg”). This two-class division may explain the strong association between certain pathogens and cancer, on one hand, and between several other pathogens and autoimmunity, on the other hand. The weak association between autoimmune diseases and HIV infection and the relatively weak association between autoimmune diseases and cancer may be elucidated as well. In addition, the model rationalizes why immune-modulating drugs, which are effective in cancer, are also effective in “high Treg” viral infections, while corticosteroids, which are generally effective in autoimmune diseases, are also effective in other “low Treg” diseases (such as asthma, atopic dermatitis, and “low Treg” infections) but are not effective in solid malignancies and “high Treg” infections. Moreover, the model expounds why certain bacteria inhibit tumor growth and why these very bacteria induce autoimmune diseases.