In previous publications, we presented the hypothesis that repeated episodes of acute or chronic psychological stress could induce an
acute phase response (APR) and subsequently a chronic inflammatory process such as
atherosclerosis. In this paper, that hypothesis, namely that such stress can induce an APR and
inflammation, has been extended to include a chronic inflammatory process(s), characterized by the presence of certain
cytokines and
acute phase reactants (APR), which is associated with certain
metabolic diseases. The loci of origin of these
cytokines, particularly
interleukin 6 (IL-6), and their induction, has been considered. Evidence is presented that the liver, the endothelium, and fat cell depots are the primary sources of
cytokines, particularly
IL-6, and that
IL-6 and the
acute phase protein (APP),
C-reactive protein (CRP), are strongly associated with, and likely play a dominant role in, the development of this inflammatory process which leads to
insulin resistance,
non-insulin dependent diabetes mellitus type II, and
Metabolic syndrome X. The possible role of psychological stress and the major stress-related
hormones as etiologic factors in the pathogenesis of these
metabolic diseases, as well as
atherosclerosis, is discussed. The fact that stress can activate an APR, which is part of the innate immune inflammatory response, is evidence that the inflammatory response is contained within the stress response or that stress can induce an inflammatory response. The evidence that the stress, inflammatory, and immune systems all evolved from a single cell, the phagocyte, is further evidence for their intimate relationship which almost certainly was maintained throughout evolution.